Glioblastoma-Infiltrating CD8+ T Cells Are Predominantly a Clonally Expanded GZMK+ Effector Population.

Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8+ T-cell population in GBM TIL. These data suggest that GZMK+ effector T cells represent an important T-cell subset within the GBM microenvironment and may harbor potential therapeutic implications. SIGNIFICANCE: To understand the limited efficacy of immune-checkpoint blockade in GBM, we applied a multiomics approach to understand the TIL landscape. By highlighting the enrichment of GZMK+ effector T cells and the lack of exhausted T cells, we provide a new potential mechanism of resistance to immunotherapy in GBM. This article is featured in Selected Articles from This Issue, p. 897.

Spontaneous rupture of an arachnoid cyst in an adult: illustrative case.

BACKGROUND: Arachnoid cysts are common intracranial mass lesions frequently discovered as incidental findings on radiographic imaging. It is routine practice to monitor these lesions as a large majority remain stable. Although traumatic cyst rupture is a known risk, it is rare for patients to present with spontaneous rupture. OBSERVATIONS: The authors report the case of a 32-year-old patient who required emergent neurosurgical intervention for spontaneous rupture of a left hemispheric arachnoid cyst. LESSONS: Patients with ruptured arachnoid cysts can present with vague, nonspecific symptoms that may delay diagnosis. If not diagnosed and treated promptly, arachnoid cyst rupture can progress to a neurosurgical emergency as the subdural collection may cause extensive mass effect and even cerebral herniation.

Economic Trends in Commonly Used Drugs for Spinal Fusion and Brain Tumor Resection: An Analysis of the Medicare Part D Database.

With the incidence of central and peripheral nervous system disorders on the rise, neurosurgical procedures paired with the careful administration of select medications have become necessary to optimize patient outcomes. Despite efforts to decrease the over-prescription of common addictive drugs, such as opioids, prescription costs continue to rise. This study analyzed temporal trends in medication use and cost for spinal fusion and brain tumor resection procedures. The Medicare Part B Database was queried from 2016 to 2020 for data regarding spinal fusion and brain tumor resection procedures, while the Part D Database was used to extract data for two commonly prescribed medications for each procedure. Pearson's correlation coefficient and linear regression were completed for the analyzed variables. The results showed a significant negative correlation between the number of spinal procedure beneficiaries and the cost of methocarbamol, as well as between the annual percent change in spinal beneficiaries and the annual percent change in oxycodone cost. Linear regression revealed that oxycodone cost was the only parameter with a statistically significant model. Moving forward, it is imperative to combat rising drug costs, regardless of trends seen in their usage. Further studies should focus on the utilization of primary data in a multi-center study.

5-ALA fluorescence-guided resection of a recurrent anaplastic pleomorphic xanthoastrocytoma: illustrative case.

BACKGROUND: 5-aminolevulinic acid (5-ALA)-induced fluorescence of neoplastic tissue is known to occur in a number of high-grade gliomas. This fluorescence helps surgeons maximize safe resection by distinguishing previously indiscernible neoplastic tissue from brain parenchyma. Still, the effectiveness of 5-ALA has not been fully explored for all central nervous system tumors. Consequently, the full spectrum of tumors that would benefit from fluorescence-guided surgery using 5-ALA is unknown. OBSERVATIONS: This report describes successfully utilizing 5-ALA to achieve complete resection of a recurrent anaplastic pleomorphic xanthoastrocytoma (APXA). LESSONS: APXA tumor cells accumulate sufficient amounts of 5-ALA and its fluorescent metabolite to produce visible intraoperative fluorescence. However, further investigation is needed to determine if 5-ALA fluorescent labeling routinely occurs in patients with APXAs.

Surgical management of an abscess of the insula.

Background: Mass lesions within the insular are diagnostically and surgically challenging due to the numerous critical cortical, subcortical, and vascular structures surrounding the region. Two main surgical techniques - the transsylvian approach and the transcortical approach - provide access to the insular cortex. Of the range of pathologies encountered, abscesses in the insula are surprisingly rare. Case Description: A 34-year-old patient was admitted for surgical resection of a suspected high-grade glioma in the insula of the dominant hemisphere. A rapid clinical decline prompted emergent neurosurgical intervention using a transsylvian approach. Surprisingly, abundant purulent material was encountered on entering the insular fossa. Pathological analysis confirmed an insular abscess, although a source of infection could not be identified. The patient required a second evacuation for reaccumulation of the abscess and adjuvant corticosteroids for extensive cerebral edema. Conclusion: An abscess located in the insular cortex is an incredibly rare occurrence. Surgical management using the transsylvian approach is one option to approach this region. Familiarity with this approach is thus extremely beneficial in situations requiring emergent access to the dominant insula when awake mapping is not feasible. In addition, treatment of abscesses with adjuvant corticosteroids is indicated when extensive, life-threatening cerebral edema is present.

Optimizing Actigraphic Estimation of Sleep Duration in Suspected Idiopathic Hypersomnia.

STUDY OBJECTIVES: To determine the optimal Actiwatch 2 setting configuration for the estimation of total sleep time (TST) in persons with suspected idiopathic hypersomnia. METHODS: Thirty-three patients with a diagnosis of idiopathic hypersomnia (28 female; mean age = 33.7 ± 10.5) underwent ad libitum polysomnography with concurrent use of the Actiwatch 2. Actiwatch 2 sleep-wake activity threshold (SWAT; Low, Medium, and High) and sleep immobility onset and offset (SIOO; 5, 10, 15, 20, 25, and 30 epoch) duration were modified during data processing. The resultant 18 unique setting combinations were subsequently evaluated using Bland-Altman and epoch comparison analyses to determine optimal settings relative to polysomnography. RESULTS: Low SWAT + 25 Epoch SIOO displayed the least divergence from polysomnography (mean difference 3.4 minutes). Higher SWAT and lower SIOO increased sensitivity and accuracy, but at the expense of reducing specificity and the ability to accurately estimate TST. CONCLUSIONS: These results demonstrate that actigraphic settings should be carefully considered when estimating sleep duration. The Low + 25 Epoch configuration is indicated as most optimal for estimating TST in persons with suspected idiopathic hypersomnia. COMMENTARY: A commentary on this article appears in this issue on page 539.