Minimally Invasive Technique for Chiari I Decompression Without Durotomy: Surgical Technique and Preliminary Case Series.

BACKGROUND: Chiari I malformation, marked by severe headaches and potential brainstem/spinal cord issues, often requires surgical intervention when conservative methods fail. This study introduces a minimally invasive surgery (MIS) Chiari decompression technique utilizing a 3-blade retractor, aiming to reduce postoperative discomfort and optimize outcomes. METHODS: Chiari type I malformation patients who underwent a MIS technique were included. Technique consisted of a minimal-soft tissue opening using a 3-blade retractor, suboccipital craniectomy, C1 laminectomy, and resection of the atlantooccipital band without a durotomy. RESULTS: Ten patients were treated. Mean age was 43.3 years, with 7 female patients. All patients presented with occipital headaches; 50% retroorbital pain; 40% neck, upper back, or shoulder pain; and 30% limb paresthesias. Median pre-surgical modified Rankin Scale (mRS) was 3 (2-4) and pain visual analog score (VAS) was 7 (5-9). Mean operative time was 59 (59-71) minutes, with mean blood loss of 88.5 (50-140) mL. In our sample, 90% of patients were discharged the same surgical day (mean 7.2 [5.3-7.7] hours postoperative). No immediate or delayed postoperative complications were evidenced. At 6 months, 90% of patients had mRS 0-1. At last follow-up the mean VAS was 1.5 (range: 0-4, P < 0.001). CONCLUSIONS: The MIS 3-blade flexible retractor technique for Chiari decompression is feasible, provides wide visualization angles of the suboccipital region and C1 arch, allows 2-surgeon work, and minimizes skin and soft tissue disruption. This combination may diminish postoperative discomfort, reduce the risk of surgical site infections, and optimize outcomes.

Transcranial Doppler emboli monitoring for stroke prevention after flow diverting stents.

OBJECTIVE: Flow diverting stents (FDS) are increasingly used for the treatment of intracranial aneurysms. While FDS can provide flow diversion of parent vessels, their high metal surface coverage can cause thromboembolism. Transcranial Doppler (TCD) emboli monitoring can be used to identify subclinical embolic phenomena after neurovascular procedures. Limited data exists regarding the use of TCDs for emboli monitoring in the periprocedural period after FDS placement. We evaluated the rate of positive TCDs microembolic signals and stroke after FDS deployment at our institution. METHODS: We retrospectively evaluated 105 patients who underwent FDS treatment between 2012 and 2016 using the Pipeline stent (Medtronic, Minneapolis, MN, USA). Patients were pretreated with aspirin and clopidogrel. All patients were therapeutic on clopidogrel pre-operatively. TCD emboli monitoring was performed immediately after the procedure. Microembolic signals (mES) were classified as "positive" (<15 mES/hour) and "strongly positive" (>15 mES/hour). Clinical stroke rates were determined at 2-week and 6-month post-operatively. RESULTS: A total of 132 intracranial aneurysms were treated in 105 patients. TCD emboli monitoring was "positive" in 11.4% (n=12) post-operatively and "strongly positive" in 4.8% (n=5). These positive cases were treated with heparin drips or modification of the antiplatelet regimen, and TCDs were repeated. Following medical management modifications, normalization of mES was achieved in 92% of cases. The overall stroke rates at 2-week and 6-months were 3.8% and 4.8%, respectively. CONCLUSIONS: TCD emboli monitoring may help early in the identification of thromboembolic events after flow diversion stenting. This allows for modification of medical therapy and, potentially, preventionf of escalation into post-operative strokes.

Head-Mounted Augmented Reality in the Planning of Cerebrovascular Neurosurgical Procedures: A Single-Center Initial Experience.

BACKGROUND: Augmented reality (AR) technology has played an increasing role in cerebrovascular neurosurgery over the last 2 decades. Hence, we aim to evaluate the technical and educational value of head-mounted AR in cerebrovascular procedures. METHODS: This is a single-center retrospective study of patients who underwent open surgery for cranial and spinal cerebrovascular lesions between April and August 2022. In all cases, the Medivis Surgical AR platform and HoloLens 2 were used for preoperative and intraoperative (preincision) planning. Surgical plan adjustment due to the use of head-mounted AR and subjective educational value of the tool were recorded. RESULTS: A total of 33 patients and 35 cerebrovascular neurosurgical procedures were analyzed. Procedures included 12 intracranial aneurysm clippings, 6 brain and 1 spinal arteriovenous malformation resections, 2 cranial dural arteriovenous fistula obliterations, 3 carotid endarterectomies, two extracranial-intracranial direct bypasses, two encephaloduroangiosynostosis for Moyamoya disease, 1 biopsy of the superficial temporal artery, 2 microvascular decompressions, 2 cavernoma resections, 1 combined intracranial aneurysm clipping and encephaloduroangiosynostosis for Moyamoya disease, and 1 percutaneous feeder catheterization for arteriovenous malformation embolization. Minor changes in the surgical plan were recorded in 16 of 35 procedures (45.7%). Subjective educational value was scored as "very helpful" for cranial, spinal arteriovenous malformations, and carotid endarterectomies; "helpful" for intracranial aneurysm, dural arteriovenous fistulas, direct bypass, encephaloduroangiosynostosis, and superficial temporal artery-biopsy; and "not helpful" for cavernoma resection and microvascular decompression. CONCLUSIONS: Head-mounted AR can be used in cerebrovascular neurosurgery as an adjunctive tool that might influence surgical strategy, enable 3-dimensional understanding of complex anatomy, and provide great educational value in selected cases.

Robotically-assisted neuro-endovascular procedures: Single-Center Experience and a Review of the Literature.

INTRODUCTION: Robotics could expand treatment of rapidly progressive pathologies such as acute ischemic stroke, with the potential to provide populations in need prompt access to neuro-endovascular procedures. METHODS: Robotically-assisted (RA) neuro-endovascular procedures (RANPs) performed at our institution were retrospectively examined (RA-group, RG). A control group of manual neuro-endovascular procedures was selected (manual group, MG). Total operating room (OR) time, procedural time, contrast media use, fluoroscopy time, conversion from RA to manual control, procedural success, and complication rates were compared. A learning curve was identified. RESULTS: Forty-one (41) RANPs were analyzed. Ages ranged from 20-82 y.o. Indications included diagnostic cerebral angiography (37), extracranial carotid artery stenting (3), and transverse sinus stent (1). Total OR time was longer in RG (median 86 vs. 71 min, p < 0.01). Procedural time (median 56 vs. 45 min, p = 0.12), fluoroscopy time (median 12 vs. 12 min, p = 0.69) and contrast media usage (82 vs. 92 ml, p = 0.54) were not significantly different. Patient radiation exposure was similar, considering similar fluoroscopy times. Radiation exposure and lead apron use were virtually absent for the main surgeon in RG. Procedural success was 83% and conversion from RA to manual control was 17% in RG. No treatment-related complications occurred. A learning curve showed that, after the fifth procedure, procedural times reduced and stabilized. CONCLUSIONS: This series may contribute to further demonstrating the safety and feasibility of RANPs. RANPs can potentially reduce radiation exposure and physical burden for health personnel, expand acute cerebrovascular treatment to underserved areas, and enhance telementoring. Prospective studies are necessary for results to be generalized.

Vertebral-Venous fistulas: Single center experience and practical treatment approach.

BACKGROUND: Vertebral-venous fistulas (VVFs) are rare. Scarce literature exists to guide our understanding and management. We report our experience and propose a classification based on flow, feeder number, and involvement of accessible veins. Additionally, we include a practical treatment approach. METHODS: Retrospective chart and imaging review of cerebrovascular arteriovenous fistulas treated in our center between July 2013 and April 2022. We reviewed patient demographics, presentation, imaging, treatment strategies, and outcomes. RESULTS: Nine patients with VVFs were identified, six were females. Ages ranged between 38-83 years. There were six high-flow and three low-flow. Most VVFs originated at the level of V3. Additional feeders from the internal carotid artery, external carotid artery, and/or subclavian artery were present in four cases (two were high-flow). Four cases had multiple arterial feeders. All cases were symptomatic. Origin was spontaneous in eight and iatrogenic in one case. Most common presenting symptoms were pain (7) and pulsatile tinnitus (4). Neurological deficits were present in two cases (1 high- and 1 low-flow). Four cases were treated with vertebral artery segmental sacrifice alone, three required multiple transarterial embolizations with or without VA sacrifice, one case had single transvenous approach, and one was treated with single targeted transarterial embolization. One patient had a minor transient neurological complication. No treatment-related mortality was seen. CONCLUSION: Treatment of high-flow and symptomatic low-flow VVFs is feasible and safe. Our classification and treatment approach might help guide patient selection and choice of endovascular approach. However, our approach warrants further validation with a larger number of patients.

Advancing neurosurgical education in the age of online learning and global knowledge sharing: impact of Cerebrovascular Q&A webinar series.

Background: The Seattle Science Foundation created the Cerebrovascular Q&A series as a free web-based tool to educate physicians and physicians-in-training about cerebrovascular and endovascular neurosurgery across geographical boundaries and different levels of training. Objective: This study aims to assess the educational impact and clinical implications of the Cerebrovascular Q&A webinar series, hosted by the Seattle Science Foundation. Methods: A digital anonymous, self-administered survey was sent to the live webinar participants. The survey contained questions about the socio-demographic characteristics of the participants, their perception of the content of the webinar series, and its impact on academic and clinical practice. The data collected from the Survey-Monkey platform was exported to Microsoft Excel which was used to perform all statistical analyses. The viewer metrics on Zoom and YouTube were also analyzed to understand trends observed among a diverse global cohort of participants. Result: A total of 2,057 people hailing from 141 countries had registered for the Cerebrovascular Q&A series. The response rate to the questionnaire was 12.63% (n = 260). Respondents hailed from 65 countries, of which the majority were from India (13.46%, n = 35) and United States (11.15%, n = 29). Most of the participants were male (82.69%, n = 215), while only 15.77% (n = 41) were female. The maximum number of participants were neurosurgery attendings (36.65%, n = 92) followed by neurosurgeons undergoing fellowship training (24.70%, n = 62) and students who were currently in residency training (15.54%, n = 39). 75.97% (n = 196) heard of the Cerebrovascular Q&A series through the emails from Seattle Science Foundation. 21.5% (n = 56) learned about the webinar series through social media. 75% of participants reported that the webinar content was advanced and comprehensive, and the selection of speakers was relevant. 63.08% (n = 164) found the webinars sparked innovative research ideas. Additionally, 55% (n = 143) reported changes in their clinical practice based on the acquired knowledge. Conclusion: The findings from this study reveal that webinar-based medical education in cerebrovascular neurosurgery is highly effective and influential. Web-based platforms and social media present a potent strategy to overcome barriers, emphasizing the need for targeted efforts to engage more women in medicine and neurosurgery recruitment.

Impact of tracheostomy timing on outcome after severe head injury.

BACKGROUND: The influence of tracheostomy timing on outcome after severe head injury remains controversial. METHODS: The investigation was based on data prospectively collected by the Pennsylvania Trauma Society Foundation statewide trauma registry from January 1990 until December 2005. RESULTS: 3,104 patients met criteria for inclusion in the study (GCS ≤ 8 and tracheostomy). Early Tracheostomy Group (ETG) patients, defined as tracheostomy performed during hospital days 1-7, were more likely to be functionally independent at discharge (adjusted odds ratio (OR) 1.45, 95% confidence interval (CI), 1.16-1.82, P = 0.001) and have a shorter length of stay (adjusted OR 0.23, 95% CI, 0.20-0.28, P < 0.0001). However, Late Tracheostomy Group (LTG) patients, defined as tracheostomy performed >7 days after admission, were approximately twice as likely to be discharged alive (adjusted OR 2.12, 95% CI, 1.60-2.82, P < 0.0001). Using a Composite Outcome Scale, which combined these three measures, there was a non-significant trend toward a higher likelihood of a poor outcome in LTG patients. When this analysis was repeated using only those patients in relatively good condition on admission, LTG patients were found to be approximately 50% less likely to have a good outcome (adjusted OR 0.46, 95% CI, 0.28-0.73, P = 0.001) when compared to ETG patients. CONCLUSIONS: These results indicate a complex relationship between tracheostomy timing and outcome, but suggest that a strategy of early tracheostomy, particularly when performed on patients with a reasonable chance of survival, results in a better overall clinical outcome than when the tracheostomy is performed in a delayed manner.

Quality and Clinical Care Development in Spine Surgery-Connecting the Dots: An Expanded Clinical Narrative.

Our health care system is an evidenced-based quality-centric environment. Pursuit of quality is a process that encompasses knowledge development and care advancements through collaboration and expertise. Depicted here is the foundational knowledge, process, and contributions that hallmark successful clinical quality programs. Beginning with methodology, followed by process and form, we create the foundational knowledge and exemplars demonstrating framework and continuum of process in pursuit and attainment of successful clinical quality and care development for patients. Although our protocol has been devised for complex spine care, this could be implemented across all health care specialties to provide individualized and high-quality care for all current and future patients, all while creating a culture of accountability for physicians.

Internal Thoracic Artery to Middle Cerebral Artery Bypass Surgery: Cadaveric Feasibsility Study.

BACKGROUND: A few options of extracranial donor vessels exist for use in intracranial vascular bypass procedures. To our knowledge, the use of an internal thoracic artery for cerebral revascularization has not been studied previously. Hence, this cadaveric feasibility study was performed. METHODS: The internal thoracic artery was dissected in 5 adult cadaveric specimens. The proximal diameter, distal diameter, and length of the vessel were measured and recorded. The artery was then transected distally at the seventh intercostal space and transposed cranially, through a pterional craniotomy opening to reach the middle cerebral artery at the skull base. RESULTS: The mean diameter of the internal thoracic artery at its proximal end was 3.5 mm and at its distal end was 2 mm. The average length of the vessel was 31 cm. There was no statistical difference between the measurements recorded from different sides or sexes. In each specimen, an internal thoracic artery was dissected, rotated superiorly, and advanced subcutaneously behind the ear to reach the middle cerebral artery at the skull base without difficulty and remained tensionless at the site of anastomosis. CONCLUSIONS: In this cadaveric study, we demonstrated the suitability of the internal thoracic artery in use as a donor vessel for a single site anastomosis in a high-flow cerebral bypass procedure.

Left Internal Carotid Artery Arising from the Right Cavernous Internal Carotid Artery: A Case Report.

Anatomical variations involving the internal carotid artery are uncommon. Herein, we present a very rare origin of the internal carotid artery. An adult female presented to the emergency department after falling. Imaging revealed that the left internal carotid artery arose from the contralateral cavernous segment of the internal carotid artery. Such a variation should be kept in mind by radiologists and surgeons who interpret and operate in this area, respectively.

Transsulcal microsurgical approach for subcortical small brain lesions: technical note.

We describe a transsulcal microsurgical approach for removal of small subcortical brain lesions, guided by frameless stereotaxy. This technique of simultaneous stereotactic localization of the subcortical lesion and its adjacent sulcus, before surgical approach, results in optimal surgical planning, leading to minimal brain tissue loss and excellent surgical outcome.

Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis.

IMPORTANCE: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies. OBJECTIVE: To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM. DATA SOURCES: Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015. STUDY SELECTION: Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines. MAIN OUTCOME AND MEASURES: Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year. RESULTS: The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low. CONCLUSION AND RELEVANCE: This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.

Onyx-HD 500 Embolization of a Traumatic Internal Carotid Artery Pseudoaneurysm after Transsphenoidal Surgery.

BACKGROUND AND PURPOSE: Traumatic intracranial pseudoaneurysms present a challenge for treatment. Traditionally these lesions have required a deconstructive approach consisting of vessel sacrifice since their fragile nature often makes direct microsurgical repair or coil embolization hazardous. As a high-viscosity liquid embolic agent that results in immediate, vessel sparing aneurysm occlusion, Onyx-HD 500 represents a uniquely efficacious tool for this clinical situation. CASE SUMMARY: We report the case of a 56-year-old right-handed gentleman who suffered a vascular injury to the ICA during revision transsphenoidal surgery for a recurrent pituitary macroadenoma. The patient was initially treated with nasal packing, but after recurrent episodes of epistaxis and a CT angiogram demonstrating a large traumatic ICA pseudoaneurysm, the patient was referred for invasive treatment. Given the presumed fragility of the lesion, embolization with Onyx-HD 500 was chosen in order to safely achieve immediate aneurysm occlusion without the need for vessel sacrifice. After an early recurrence due to incomplete initial embolization, the patient went on to complete occlusion without further hemorrhage. CONCLUSION: This case illustrates the utility of a high-viscosity liquid embolic agent in providing immediate protection from rehemorrhage by occluding a large ruptured pseudoaneurysm of the proximal intracranial ICA, while sparing the parent artery.

Pure neuritic leprosy presenting as ulnar nerve neuropathy: a case report of electrodiagnostic, radiographic, and histopathological findings.

Hansen's disease, or leprosy, is a chronic infectious disease with many manifestations. Though still a major health concern and leading cause of peripheral neuropathy in the developing world, it is rare in the United States, with only about 150 cases reported each year. Nevertheless, it is imperative that neurosurgeons consider it in the differential diagnosis of neuropathy. The causative organism is Mycobacterium leprae, which infects and damages Schwann cells in the peripheral nervous system, leading first to sensory and then to motor deficits. A rare presentation of Hansen's disease is pure neuritic leprosy. It is characterized by nerve involvement without the characteristic cutaneous stigmata. The authors of this report describe a case of pure neuritic leprosy presenting as ulnar nerve neuropathy with corresponding radiographic, electrodiagnostic, and histopathological data. This 11-year-old, otherwise healthy male presented with progressive right-hand weakness and numbness with no cutaneous abnormalities. Physical examination and electrodiagnostic testing revealed findings consistent with a severe ulnar neuropathy at the elbow. Magnetic resonance imaging revealed diffuse thickening and enhancement of the ulnar nerve and narrowing at the cubital tunnel. The patient underwent ulnar nerve decompression with biopsy. Pathology revealed acid-fast organisms within the nerve, which was pathognomonic for Hansen's disease. He was started on antibiotic therapy, and on follow-up he had improved strength and sensation in the ulnar nerve distribution. Pure neuritic leprosy, though rare in the United States, should be considered in the differential diagnosis of those presenting with peripheral neuropathy and a history of travel to leprosy-endemic areas. The long incubation period of M. leprae, the ability of leprosy to mimic other conditions, and the low sensitivity of serological tests make clinical, electrodiagnostic, and radiographic evaluation necessary for diagnosis. Prompt diagnosis and treatment is imperative to prevent permanent neurological injury.

Surgical advances for extracranial carotid stenosis.

Carotid endarterectomy is a commonly performed operation to prevent stroke in patients who have asymptomatic or symptomatic internal carotid artery atherosclerotic stenosis. Carotid angioplasty and stenting has also been advocated for treatment of these patients. In this article, we address a number of questions for which a review of available data will advance our understanding of the role of carotid endarterectomy in stroke prevention. These include the following: Are carotid endarterectomy and carotid angioplasty and stenting equivalent procedures for the treatment of carotid artery disease? Which patients should be deemed at high risk for carotid endarterectomy? Should carotid endarterectomy be an urgent procedure in symptomatic patients with severe internal carotid artery stenosis? Finally, what is the role of carotid endarterectomy in asymptomatic patients? We also review the senior author's personal experience with >2000 consecutive carotid endarterectomies, with special attention to his present approach to this operation. We believe that carotid endarterectomy, in experienced hands, is a minimally invasive operation that remains the procedure of choice for most patients with carotid artery disease who will benefit from invasive treatment.

Characterization of a novel anti-cancer compound for astrocytomas.

The standard chemotherapy for brain tumors is temozolomide (TMZ), however, as many as 50% of brain tumors are reportedly TMZ resistant leaving patients without a chemotherapeutic option. We performed serial screening of TMZ resistant astrocytoma cell lines, and identified compounds that are cytotoxic to these cells. The most cytotoxic compound was an analog of thiobarbituric acid that we refer to as CC-I. There is a dose-dependent cytotoxic effect of CC-I in TMZ resistant astrocytoma cells. Cell death appears to occur via apoptosis. Following CC-I exposure, there was an increase in astrocytoma cells in the S and G2/M phases. In in vivo athymic (nu/nu) nude mice subcutaneous and intracranial tumor models, CC-I completely inhibited tumor growth without liver or kidney toxicity. Molecular modeling and enzyme activity assays indicate that CC-I selectively inhibits topoisomerase IIα similar to other drugs in its class, but its cytotoxic effects on astrocytoma cells are stronger than these compounds. The cytotoxic effect of CC-I is stronger in cells expressing unmethylated O6-methylguanine methyltransferase (MGMT) but is still toxic to cells with methylated MGMT. CC-I can also enhance the toxic effect of TMZ on astrocytoma when the two compounds are combined. In conclusion, we have identified a compound that is effective against astrocytomas including TMZ resistant astrocytomas in both cell culture and in vivo brain tumor models. The enhanced cytotoxicity of CC-I and the safety profile of this family of drugs could provide an interesting tool for broader evaluation against brain tumors.

COX-2 drives metastatic breast cells from brain lesions into the cerebrospinal fluid and systemic circulation.

Breast cancer is among the most common malignancies that metastasize to the brain, with 15% to 20% of patients with metastatic breast cancer eventually developing brain metastases. We previously reported a method to enumerate tumor cells in the cerebrospinal fluid (CSF) of patients with breast cancer with central nervous system (CNS) metastases, a setting that lacks sufficiently informative biomarkers. Here, we show that breast cancer cells can spontaneously disseminate into the CSF from brain lesions in mice in a COX-2-dependent manner and can escape from the CNS to systemic circulation. Enumeration of tumor cells in the peripheral blood (circulating tumor cells, CTC) and CSF (cerebrospinal fluid tumor cells, CSFTC) of nine breast cancer patients with brain metastases revealed dynamic changes in tumor cell burden in both the peripheral blood and CSF compartments that correlated with clinical disease progression. Interestingly, four of the enrolled patients exhibited rapid intercompartmental transitioning of the disease reflected in the CTC and CSFTC counts that preceded corresponding evidence by clinical imaging or neurologic symptoms. Two of these patients had systemic disease recurrence involving the primary malignant site. Intercompartmental cycling of tumor cells may represent an important mechanism for disease persistence and recurrence that may involve tumor self-seeding. Our findings demonstrate the involvement of COX-2 in the genesis of CSFTCs and suggest that COX-2 inhibitors should be investigated in patients with breast cancer with brain metastases for their ability to reduce CSFTC counts and prevent systemic recurrence.

Detection of circulating tumor cells in the cerebrospinal fluid of a patient with a solitary metastasis from breast cancer: A case report.

Brain lesions identified following the diagnosis and eradication of primary cancers are often ambiguous in origin, existing as a solitary metastasis or an independent primary brain tumor. The brain is a relatively common site of metastasis with breast cancer, although determining whether metastases have originated from the breast or brain is often not possible without invasive biopsies. In the current case report, a patient presented with a brain lesion identified by radiography and was without systemic disease. The patient had previously exhibited a complete response to chemotherapy and surgery for a poorly differentiated invasive ductal carcinoma. The origin of the brain lesion could not be determined by magnetic resonance imaging, giving rise to a diagnostic dilemma with diverging treatment options. We previously reported a method to isolate and enumerate tumor cells of epithelial origin in the cerebrospinal fluid (CSF). CSF tumor cell analysis of the patient revealed massive CSF tumor cell burden of epithelial origin, indicating that the brain lesion was likely of breast origin. The current case report highlights the use of CSF tumor cell detection as a differential diagnostic tool, in addition to its previously demonstrated use as a marker of disease burden and therapeutic response.

Endovascular embolization by parent artery reconstruction of a symptomatic fusiform posterior cerebral artery aneurysm using Onyx HD-500: a neurointerventional report.

BACKGROUND AND PURPOSE: Posterior cerebral artery aneurysms are treatment challenge for the neurosurgeon. Parent artery occlusion, trapping and bypass have been the classic treatment options for aneurysms in this location. With the introduction of newer embolic agents such as Onyx®, endovascular intervention is now a viable therapy for these aneurysms. CASE SUMMARY: We report the case of a 60-year-old man who presented with a symptomatic, though unruptured, fusiform left posterior cerebral artery aneurysm. Given the distal location of this dominant sided aneurysm, post-operative visual deficits and aphasia were a concern if parent vessel occlusion were to be performed. Therefore, an endovascular reconstruction using Onyx HD-500 and two closed-cell stents was performed. CONCLUSIONS: This report illustrates the ability of a high-density liquid embolic agent to provide immediate reconstruction of a fusiform aneurysm in a distal location.

Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.

Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an antitumor protein that is in clinical trials as a potential anticancer therapy but suffers from drug properties that may limit efficacy such as short serum half-life, stability, cost, and biodistribution, particularly with respect to the brain. To overcome such limitations, we identified TRAIL-inducing compound 10 (TIC10), a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier. TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10. TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.