Panayiotis Pelargos

Utilizing virtual and augmented reality for educational and clinical enhancements in neurosurgery

Neurosurgery has undergone a technological revolution over the past several decades, from trephination to image-guided navigation. Advancements in virtual reality (VR) and augmented reality (AR) represent some of the newest modalities being integrated into neurosurgical practice and resident education. In this review, we present a historical perspective of the development of VR and AR technologies, analyze its current uses, and discuss its emerging applications in the field of neurosurgery.

Transferrin receptors and glioblastoma multiforme: Current findings and potential for treatment

The current standard treatment for glioblastoma multiforme (GBM) is surgery followed by chemotherapy and external radiation. Even with the standard treatment, the 2 year survival rate for GBM is less than 20%, making research for alternative treatments necessary. Transferrin receptor 1 (TfR1) controls the rate of cellular iron uptake by tuning the amount of iron delivered to the cells to meet metabolic needs. Kawabata et al. (J Biol Chem 1999;274:20826-32) cloned a second TfR molecule known as transferrin receptor 2 (TfR2) in 1999. Multiple experimental studies have documented increased expression of TfR1 on both proliferating cells and cells that have undergone malignant transformation. Calzolari et al. concluded that TfR2 is frequently expressed in human cell lines in 2007 (Blood Cells Mol Dis 2007;39:82-91) and in GBM in particular in 2010 (Transl Oncol 2010;3:123-34). In GBM, a highly significant correlation (p<0.0001) was found between the expression level of TfR2 and overall survival, showing that higher levels of TfR2 expression were associated with an overall longer survival. The data on which of the two transferrin receptors is the better target is also unclear and should be studied. The transferrin pathway may be a promising target, but more research should be completed on the antigenicity to discern the viability of it as an immunotherapy target.

Clinical outcomes of middle fossa craniotomy for superior semicircular canal dehiscence repair

OBJECTIVE Superior semicircular canal dehiscence (SSCD) is a rare disorder characterized by the formation of a third opening in the inner ear between the superior semicircular canal and the middle cranial fossa. Aberrant communication through this opening causes a syndrome of hearing loss, pulsatile tinnitus, disequilibrium, and autophony. This study analyzed the clinical outcomes of a single-institution series of patients with SSCD undergoing surgical repair by the same otolaryngologist and neurosurgeon. METHODS All patients who underwent SSCD repair at the University of California, Los Angeles, between March 2011 and November 2014 were included. All patients had their SSCD repaired via middle fossa craniotomy by the same otolaryngologist and neurosurgeon. Outcomes were analyzed with Fishers exact test. RESULTS A total of 18 patients with a mean age of 56.2 years (range 27-84 years) and an average follow-up of 5.0 months (range 0.2-21.8 months) underwent 21 cases of SSCD repair. Following treatment, all patients (100%) reported resolution in ≥ 1 symptom associated with SSCD. Autophony (p = 0.0005), tinnitus (p = 0.0059), and sound- and/or pressure-induced dizziness (p = 0.0437) showed significant symptomatic resolution. Following treatment, 29% (2/7) of patients developed imbalance, 20% (1/5) of patients developed sound- and/or pressure-induced dizziness, and 18% (2/11) of patients developed aural fullness. Among patients with improved symptoms following surgical repair, none reported recurrence of symptoms at subsequent follow-up visits. CONCLUSIONS SSCD remains an underdiagnosed and undertreated condition. Surgical repair of SSCD using a middle fossa craniotomy is associated with a high rate of symptom resolution. Continued investigation using a larger patient cohort and longer-term follow-up could further demonstrate the effectiveness of using middle fossa craniotomy for SSCD repair.

The role of CD44 in glioblastoma multiforme

A transmembrane molecule with several isoforms, CD44 is overexpressed in many tumors and promotes tumor formation through interactions with the tumor microenvironment. CD44 has been implicated in malignant processes including cell motility, tumor growth, and angiogenesis. The role of CD44 has been examined in many cancer types. This paper provides, to our knowledge, the first focused review of the role of CD44 in glioblastoma multiforme (GBM), the most common and fatal of primary brain cancers. We summarize research that describes how CD44 promotes GBM aggressiveness by increasing tumor cell invasion, proliferation and resistance to standard chemoradiation therapy. Effects of CD44 inhibition in GBM are also explored. Clinical trials investigating CD44 targeting in CD44-positive solid tumors are underway, and the evidence presented here suggests that CD44 inhibition in GBM may be a promising therapy.

Laser neurosurgery: A systematic analysis of magnetic resonance-guided laser interstitial thermal therapies

Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel minimally invasive modality that uses heat from laser probes to destroy tissue. Advances in probe design, cooling mechanisms, and real-time MR thermography have increased laser utilization in neurosurgery. The authors perform a systematic analysis of two commercially available MRgLITT systems used in neurosurgery: the Visualase® thermal therapy and NeuroBlate® Systems. Data extraction was performed in a blinded fashion. Twenty-two articles were included in the quantitative synthesis. A total of 223 patients were identified with the majority having undergone treatment with Visualase (n=154, 69%). Epilepsy was the most common indication for Visualase therapy (n=8 studies, 47%). Brain mass was the most common indication for NeuroBlate therapy (n=3 studies, 60%). There were no significant differences, except in age, wherein the NeuroBlate group was nearly twice as old as the Visualase group (p<0.001). Frame, total complications, and length-of-stay (LOS) were non-significant when adjusted for age and number of patients. Laser neurosurgery has evolved over recent decades. Clinical indications are currently being defined and will continue to emerge as laser technologies become more sophisticated. Head-to-head comparison of these systems was difficult given the variance in indications (and therefore patient population) and disparate literature.

A Systematic Analysis of the Reliability of Diffusion Tensor Imaging Tractography for Facial Nerve Imaging in Patients with Vestibular Schwannoma

Surgeons need to visualize the facial nerve reliably in relation to the vestibular schwannoma (VS) in surgical planning. Diffusion tensor imaging (DTI) tractography has enabled unprecedented in vivo preoperative visualization. We collected data to measure the accuracy of DTI for an accurate location of the nerve in preoperative VS resection planning. A PubMed search for relevant studies was conducted. Inclusion criteria were gross total resection of VS, preoperative DTI identification of the facial nerve, and intraoperative cranial nerve localization by the surgeon. Exclusion criteria were tumors other than VS and unsuccessful preoperative location of the cranial nerve. Accuracy rate was calculated by comparing the intraoperative and preoperative locations detailed by DTI. The query identified 38 cases of VS that fit our inclusion criteria. Overall, 89% had surgical findings that agreed with the DTI location of the facial nerve. Of these cases, 32 patients had a postoperative House-Brackmann grade I or II. Our findings suggest that DTI is a reliable method for facial nerve imaging. Implementation of this technique may help decrease facial nerve injury during surgery. Limitations and further studies are needed to better understand what factors correlate with successful location of the facial nerve and DTI in patients with VS.

Recent Advances in the Patient Safety and Quality Initiatives Movement Implications for Neurosurgery

The US health care system is fragmented in terms of quality care, costs, and patient satisfaction. With the passage of the Affordable Care Act, national attention has been placed on the health care system, but effective change has yet to be observed. Unnecessary costs, medical errors, and uncoordinated efforts contribute to patient morbidity, mortality, and decreased patient satisfaction. In addition to national efforts, local initiatives within individual departments must be implemented to improve overall satisfaction without the sacrifice of costs. In this article, the current issues with the health care system and potential initiatives for neurosurgery are reviewed.

Clinical characteristics and diagnostic imaging of cranial osteoblastoma

Benign osteoblastoma is a rare, vascular, osteoid-forming bone tumor that occurs even less frequently in the cranial bones. Benign osteoblastoma of the cranium affects women slightly more often than men and typically presents in the first three decades of life. Although clinical presentation can vary depending on location, cranial osteoblastoma usually presents as a painful, non-mobile, subcutaneous mass or swelling. On CT scan, it generally presents as a well-demarcated, mixed lytic and sclerotic lesion, with enlarged diploe, thinning outer and/or inner tables, and varying degrees of calcification. It is hypo to isointense on T1-weighted MRI and has variable presentation on T2-weighted MRI. Gross total resection is the definitive treatment, while subtotal resection is utilized when it is necessary to preserve critical adjacent neurovascular structures.

Epithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is associated with an extremely poor clinical prognosis. One pathologic hallmark of GBM is excessive vascularization with abnormal blood vessels. Extensive investigation of anti-angiogenic therapy as a treatment for recurrent GBM has been performed. Bevacizumab, a monoclonal anti-vascular endothelial growth factor A (VEGF-A), suggests a progression-free survival benefit but no overall survival benefit. Developing novel anti-angiogenic therapies are urgently needed in controlling GBM growth. In this study, we demonstrate tumor expression of epithelial membrane protein-2 (EMP2) promotes angiogenesis both in vitro and in vivo using cell lines from human GBM. Mechanistically, this pro-angiogenic effect of EMP2 was partially through upregulating tumor VEGF-A levels. A potential therapeutic effect of a systemic administration of anti-EMP2 IgG1 on intracranial xenografts was observed resulting in both significant reduction of tumor load and decreased tumor vasculature. These results suggest the potential for anti-EMP2 IgG1 as a promising novel anti-angiogenic therapy for GBM. Further investigation is needed to fully understand the molecular mechanisms how EMP2 modulates GBM pathogenesis and progression and to further characterize anti-EMP2 therapy in GBM.

Incidental Meningiomas: Management in the Neuroimaging Era

The number of patient imaging studies has increased because of precautious physicians ordering scans when a vague symptom is presented; subsequently, the number of incidental meningiomas detected has increased as well. These brain tumors do not present with related symptoms and are usually small. MRI and computed tomographic scans most frequently capture incidental meningiomas. Incidental meningiomas are managed with observation, radiation, and surgical resection. Ultimately, a conservative approach is recommended, such as observing an incidental meningioma and then only radiating if the tumor displays growth, whereas a surgical approach is to be used only when proven necessary.