Using pre-surgical suspicion to guide insula implantation strategy.

Rationale: Insular epilepsy can be a challenging diagnosis due to overlapping semiology and scalp EEG findings with frontal, temporal, and parietal lobe epilepsies. Stereotactic electroencephalography (sEEG) provides an opportunity to better localize seizure onset. The possibility of improved localization is balanced by implantation risk in this vascularly rich anatomic region. We review both safety and pre-implantation factors involved in insular electrode placement across four years at an academic medical center. Methods: Presurgical data, operative reports, and invasive EEG summaries were retrospectively reviewed for patients undergoing invasive epilepsy monitoring on the insula from 2016 through 2019. EEG reports were reviewed to record the presence of insula ictal and interictal involvement. We recorded which presurgical findings suggested insular involvement (insula lesion on MRI, insula changes on PET/SPECT/scalp EEG, characteristic semiology, or history of failed anterior temporal lobectomy). The likelihood of pre-sEEG insular onset was categorized as low suspicion if no presurgical findings were present ("rule out"), moderate suspicion if one finding was present, and high suspicion if two or more findings were present. Results: 76 patients received 189 insular electrodes as part of their implantation strategy for 79 surgical cases. Seven patients (8.9%) had insular ictal onset. One clinically significant complication (left hemiparesis) occurred in a patient with moderate suspicion for insular onset. There were 38 low suspicion cases, 36 moderate suspicion cases, and 5 high suspicion cases for pre-sEEG insula ictal onset. Two low suspicion (5.3%), three moderate suspicion (8.6%), and two high suspicion (40%) cases had insular ictal onset. Conclusions: The insula can safely receive sEEG. Having two or more presurgical factors indicating insular onset is a strong, albeit incomplete, predictor of insular seizure onset. Using pre-implantation clinical findings can offer clinicians predictive value for targeting the insula during invasive EEG monitoring.

EGFR as a potent CAR T target in triple negative breast cancer brain metastases.

PURPOSE: There is currently no curative treatment for patients diagnosed with triple-negative breast cancer brain metastases (TNBC-BM). CAR T cells hold potential for curative treatment given they retain the cytolytic activity of a T cell combined with the specificity of an antibody. In this proposal we evaluated the potential of EGFR re-directed CAR T cells as a therapeutic treatment against TNBC cells in vitro and in vivo. METHODS: We leveraged a TNBC-BM tissue microarray and a large panel of TNBC cell lines and identified elevated epidermal growth factor receptor (EGFR) expression. Next, we designed a second-generation anti-EGFR CAR T construct incorporating a clinically relevant mAb806 tumor specific single-chain variable fragment (scFv) and intracellular 4-1BB costimulatory domain and CD3ζ using a lentivirus system and evaluated in vitro and in vivo anti-tumor activity. RESULTS: We demonstrate EGFR is enriched in TNBC-BM patient tissue after neurosurgical resection, with six of 13 brain metastases demonstrating both membranous and cytoplasmic EGFR. Eleven of 13 TNBC cell lines have EGFR surface expression ≥ 85% by flow cytometry. EGFR806 CAR T treated mice effectively eradicated TNBC-BM and enhanced mouse survival (log rank p < 0.004). CONCLUSION: Our results demonstrates anti-tumor activity of EGFR806 CAR T cells against TNBC cells in vitro and in vivo. Given EGFR806 CAR T cells are currently undergoing clinical trials in primary brain tumor patients without obvious toxicity, our results are immediately actionable against the TNBC-BM patient population.

Spinal cord stimulator for the treatment of central neuropathic pain secondary to cervical syringomyelia: illustrative case.

BACKGROUND: Central neuropathic pain (CNP) of the cervical and/or thoracic spinal cord has many etiologies, both natural and iatrogenic. Frequently, CNP is medically refractory and requires surgical treatment to modulate the perception of pain. Spinal cord stimulation is a modality commonly used in adults to treat this type of refractory pain; however, it is rarely used in the pediatric population. OBSERVATIONS: The authors reported a case involving a common pediatric condition, Chiari malformation type I with syrinx, that led to a debilitating complex regional pain syndrome. The associated life-altering pain was successfully alleviated following placement of a spinal cord stimulator. LESSONS: CNP, or the syndromic manifestations of the pain (complex regional pain syndrome), can alter an individual's life in dramatic ways. Spinal cord stimulator placement in carefully selected pediatric patients should be considered in these difficult pain treatment paradigms.

sEEG for expansion of a surgical epilepsy program: Safety and efficacy in 152 consecutive cases.

OBJECTIVE: Stereoelectroencephalography (sEEG) is an intracranial encephalography method of expanding use. The need for increased epilepsy surgery access has led to the consideration of sEEG adoption by new or expanding surgical epilepsy programs. Data regarding safety and efficacy are uncommon outside of high-volume, well-established centers, which may be less applicable to newer or low-volume centers. The objective of this study was to add to the sEEG outcomes in the literature from the perspective of a rapidly expanding center. METHODS: A retrospective chart review of consecutive sEEG cases from January 2016 to December 2019 was performed. Data extraction included demographic data, surgical data, and outcome data, which pertinently examined surgical method, progression to therapeutic procedure, clinically significant adverse events, and Engel outcomes. RESULTS: One hundred and fifty-two sEEG procedures were performed on 131 patients. Procedures averaged 10.5 electrodes for a total of 1603 electrodes. The majority (84%) of patients progressed to a therapeutic procedure. Six clinically significant complications occurred: three retained electrodes, two hemorrhages, and one failure to complete investigation. Only one complication resulted in a permanent deficit. Engel 1 outcome was achieved in 63.3% of patients reaching one-year follow-up after a curative procedure. SIGNIFICANCE: New or expanding epilepsy surgery centers can appropriately consider the use of sEEG. The complication rate is low and the majority of patients progress to therapeutic surgery. Procedural safety, progression to therapeutic intervention, and Engel outcomes are comparable to cohorts from long-established epilepsy surgery programs.

Cost-Effectiveness of Adult Spinal Deformity Surgery.

STUDY DESIGN: Review article. OBJECTIVE: A review of the literature evaluating the cost-effectiveness of undergoing adult spinal deformity surgery and potential avenues for reducing costs. METHODS: A review of the current literature and synthesis of data to provide an update on the cost effectiveness of undergoing adult spinal deformity surgery. RESULTS: Compared with nonoperative management, operative management for adult spinal deformity is associated with improved patient-reported outcomes and quality of life; however, it is associated with significant financial and resource use. CONCLUSION: Operative management for adult spinal deformity has been shown to be effective but is associated with significant cost and resource utilization. The optimal operative treatment is highly dependent on the patients' symptomatology and is surgeon dependent. Maximizing preoperative surgical health and minimizing postoperative complications are key measures in reducing the cost and resource utilization of adult spinal deformity surgery. Future studies are needed to evaluate how to optimize the cost-effectiveness.

Incidence of Intracranial Melanoma Progression in the Setting of Positive Extracranial Response to Targeted Therapy and Immunotherapy: An Indication for More Frequent Screening in This Population?

Background and objective The incidence of intracranial metastases from melanoma is on the rise. In this study, we aimed to determine the incidence of intracranial disease progression in patients on BRAF/MEK targeted therapy and immunotherapy in the setting of controlled or improving extracranial disease. Methods This was a single-center, retrospective review that involved patients who underwent stereotactic radiosurgery (SRS) for intracranial metastatic melanoma between January 1, 2014, and December 31, 2018. We focused on BRAF/MEK mutation status and dates of treatment with BRAF/MEK targeted therapy, immunotherapy [ipilimumab (Yervoy), nivolumab (Opdivo), or pembrolizumab (Keytruda)], and combination targeted and immunotherapy. Results A total of 51 patients were enrolled: 36 males and 15 females. The average age of the patients was 58.6 years, and 26 among them were BRAF mutation-positive. Seventeen had prior surgery with SRS as adjuvant therapy. The other 34 had SRS as primary treatment. Forty-two patients had extracranial disease present at the time of SRS. There were 34 patients treated with targeted and immune therapy. Overall, 16 patients (47.1%) demonstrated controlled or improving extracranial disease, and 18 (52.9%) demonstrated progressing extracranial disease at the time of SRS. In the subgroup analysis, patients treated with BRAF/MEK targeted therapy demonstrated a 75% rate of extracranial disease control. The extracranial disease was controlled in 43.75% of patients on immunotherapy with intracranial progression, while it was controlled in 30% of patients on both BRAF/MEK targeted therapy and immunotherapy with intracranial progression. Sixteen patients (47.1%) developed intracranial metastasis in our study while having a stable systemic disease with BRAF/MEK targeted therapy, immunotherapy, or a combination of the two. Conclusion Based on our findings, a systemic response to targeted therapy and immunotherapy does not necessarily parallel intracranial protection.