Dr. Louise Eisenhardt's personal notes: how she and Dr. Cushing collected data and followed patients.

Dr. Louise Eisenhardt was one of the first neuropathologists and was responsible for the development of tumor diagnosis guidelines. This historical vignette reviews her previously unseen handwritten notes in which she describes methods used by her and Dr. Harvey Cushing to obtain patient follow-up data for their Brain Tumor Registry. Her description spans 50 years, using "every possible clue to be jumped upon in [their] clinical records and correspondence." Their follow-up was divided into two periods: early follow-up (1912-1932) and registry (1933-1961). During early follow-up, patients were asked to write to them on the anniversary of their operation. The foundation of the registry necessitated the use of "considerable effort on [their] part to gather up old threads" including renewed contact with patients after 15-20 years. Methods of follow-up included continued verbal and written correspondence with patients and "strong-arm methods," including use of the Fuller Brush man and the exhumation of a body. Drs. Eisenhardt and Cushing believed "every case was important in adding to our collective knowledge of various types of tumors particularly in relationship to life expectancies and suggesting improvement in surgical treatments." Dr. Eisenhardt's meticulous record keeping allows for insights into the first known outcomes-related tumor registry in neurosurgery.

A Functional Precision Medicine Pipeline Combines Comparative Transcriptomics and Tumor Organoid Modeling to Identify Bespoke Treatment Strategies for Glioblastoma.

Li Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by germline mutations in TP53. TP53 is the most common mutated gene in human cancer, occurring in 30-50% of glioblastomas (GBM). Here, we highlight a precision medicine platform to identify potential targets for a GBM patient with LFS. We used a comparative transcriptomics approach to identify genes that are uniquely overexpressed in the LFS GBM patient relative to a cancer compendium of 12,747 tumor RNA sequencing data sets, including 200 GBMs. STAT1 and STAT2 were identified as being significantly overexpressed in the LFS patient, indicating ruxolitinib, a Janus kinase 1 and 2 inhibitors, as a potential therapy. The LFS patient had the highest level of STAT1 and STAT2 expression in an institutional high-grade glioma cohort of 45 patients, further supporting the cancer compendium results. To empirically validate the comparative transcriptomics pipeline, we used a combination of adherent and organoid cell culture techniques, including ex vivo patient-derived organoids (PDOs) from four patient-derived cell lines, including the LFS patient. STAT1 and STAT2 expression levels in the four patient-derived cells correlated with levels identified in the respective parent tumors. In both adherent and organoid cultures, cells from the LFS patient were among the most sensitive to ruxolitinib compared to patient-derived cells with lower STAT1 and STAT2 expression levels. A spheroid-based drug screening assay (3D-PREDICT) was performed and used to identify further therapeutic targets. Two targeted therapies were selected for the patient of interest and resulted in radiographic disease stability. This manuscript supports the use of comparative transcriptomics to identify personalized therapeutic targets in a functional precision medicine platform for malignant brain tumors.

Decompression of Cavernous Sinus for Trigeminal Neuropathic Pain From Perineural Spread of Tumor: 2-Dimensional Operative Video.

Head and neck malignancies with perineural spread are rare. Patients can present with neuropathic pain and cranial nerve palsies.1 Skull base approaches for surgical decompression are a consideration for patients to provide symptom relief.2 We demonstrate a frontotemporal extradural approach for a patient with worsening visual symptoms and refractory neuropathic pain in the V1, V2, and V3 distributions and briefly review the relevant anatomy.3-7 A 41-yr-old female with a poorly differentiated carcinoma of the head and neck with an infiltration of the cavernous sinus and perineural spread along the trigeminal nerve presented with severe neuropathic facial pain and anesthesia. She had previously undergone radiosurgery. Magnetic resonance imaging (MRI) demonstrated an interval increase in perineural disease within the cavernous sinus with extension intradurally. Her pain was medically refractory. A 2-dimensional intraoperative video illustrates the microsurgical decompression of her perineural invasion along the skull base as a palliative procedure. The patient recovered well postoperatively and had a symptomatic improvement in her pain and visual symptoms. Her preoperative facial numbness persisted postoperatively as expected. Postoperative imaging demonstrates a gross total resection of the intradural component of the tumor with decompression and expected expansion of the cavernous sinus. Because of the retrospective nature of this report, informed consent was not required. Images within the video have been reproduced from Fukuda et al4 with permission from © Georg Thieme Verlag KG; and Matsuo et al5 by permission of the Congress of Neurological Surgeons.