Glioblastoma, the most aggressive primary brain tumor, carries a dismal prognosis, with median survival remaining under 15 months despite standard therapies. This is largely because of the tumor’s infiltrative nature, the restrictive blood–brain barrier, and intratumoral heterogeneity. Chlorotoxin (CTX), a 36-amino acid peptide derived from scorpion venom, has emerged as a promising multifunctional agent with high specificity for neuroectodermal tumors. In this comprehensive review, we highlight CTX’s potential to address critical limitations of current glioma treatments by bridging diagnostic and therapeutic modalities. Diagnostic advancements include CTX-conjugated near-IF fluorophores and nanoparticles for fluorescence-guided surgery and multimodal imaging to enhance intraoperative accuracy. On the therapeutic front, CTX enables targeted delivery of siRNA, radioisotopes, and novel immunotherapies such as CTX-directed chimeric antigen receptor T cells. We also examine emerging clinical data supporting the safety and preliminary efficacy of CTX-based interventions. Collectively, CTX represents a paradigm shift in neuro-oncology, offering a single molecule with both diagnostic and therapeutic capabilities. Its utility may also extend beyond gliomas to metastases and other malignancies within and beyond the central nervous system.

Glioblastoma (GBM) is the most common form of primary adult brain tumor with a five-year survival of <7%. Standard of care (SoC) involves maximal safe surgical resection with chemoradiation; nevertheless, most patients experience disease progression. Deep intracranial GBM is unresectable, limiting treatment to chemoradiation only. Thus, novel approaches are needed. Laser interstitial thermal therapy (LITT) is a promising minimally invasive procedure using thermal energy for focal necrosis. Another approach is antiretroviral therapy (ART), which was initially explored as a treatment for acquired immunodeficiency syndrome (AIDS)-related malignancies, that has recently shown preclinical promise for GBM. We present the Synergistic Treatment with Antiretrovirals and Laser Interstitial Thermal ThErapy (STARLITE) (NCT06428045) trial, which seeks to synergize LITT with ART to treat unresectable GBM. STARLITE is a single-institution, single-arm, phase 1 study. An ART regimen of abacavir, lamivudine, and ritonavir will be administered followed by SoC adjuvant therapy in patients with newly-diagnosed, unresectable GBM after LITT. The primary objective of the study will be the determination of the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of ritonavir as part of the ART regimen. Secondary objectives of the clinical trial will be to estimate progression-free survival (PFS) and overall survival (OS). LITT has been shown to have minimal post-operative complications while improving OS in unresectable GBM. In preclinical GBM models, ART has been shown to reduce cell viability and stemness. STARLITE aims to leverage the ability of LITT to target unresectable GBM foci and transiently open the blood-brain barrier (BBB) to increase the tumoral delivery of ART and augment its anti-tumor effects. We hypothesize this combination will be well-tolerated with minimal adverse effects and improve GBM prognosis. Trial Registration: This clinical trial is registered on ClinicalTrials.gov (NCT06428045). The authors confirm that all ongoing and related trials for this intervention are registered.

BACKGROUND: Deep pelvic peripheral nerve sheath tumors (PNSTs) present unique surgical challenges due to their proximity to critical neurovascular structures. Conventional localization techniques may result in aborted procedures or subtotal resections. OBSERVATIONS: Two patients with suspected deep PNSTs underwent MR neurography (MRN) and CT-integrated neuronavigation-guided microsurgical resection. Patient 1, a 56-year-old woman with left-sided radicular pain, had a 1.5-cm lesion adjacent to the left sciatic nerve at S2. A prior resection was aborted due to difficulty localizing the tumor. MRN/CT-integrated neuronavigation enabled accurate identification and complete resection. At 1 year, she demonstrated improved ambulation, reduced pain, and no recurrence. Patient 2, a 72-year-old woman with recurrent radicular buttock pain, harbored a 4.9-cm mass at the sciatic notch. A prior nonnavigated resection was subtotal. Reoperation with neuronavigation enabled precise delineation of tumor margins, resulting in near-complete resection and symptom improvement. LESSONS: MR-assisted neuronavigation is a valuable adjunct for intraoperative localization of deep, anatomically complex suspected PNSTs, offering enhanced precision and improved safety. While safe resection depends on microsurgical technique and nerve monitoring, navigation-guided localization may reduce aborted procedures, facilitate confident surgical planning, and minimize iatrogenic injury. Broader validation through prospective studies is warranted to define optimal applications. https://thejns.org/doi/10.3171/CASE26540

Objectives: Tandem spinal stenosis (TSS) is often underdiagnosed and traditionally managed with multi-stage surgery (MSS). Single-stage surgery (SSS) is an alternative, but prior studies largely emphasize younger, healthier patients. This study evaluated perioperative and functional outcomes after SSS for TSS in a surgically diverse cohort. Methods: A retrospective chart review included 20 patients who underwent SSS for TSS at a single academic institution. Mean age was 63.75 years, and median modified frailty index was 2. Etiologies included degenerative, traumatic, and neoplastic disease across cervical, thoracic, and lumbar regions. Outcomes included operative characteristics, complications, readmissions, and functional recovery measured by Visual Analog Scale (VAS) pain and modified Japanese Orthopaedic Association (mJOA) scores. Results: The mean number of operated levels was 5.2, mean operative time was 232.4 min, total OR time was 355.1 min, and length of stay was 6.9 days. Surgical complications occurred in 15% of patients, medical complications in 25%, and 90-day readmission in 15%, with no 30-day mortality. Mean mJOA improved from 12.86 at baseline to 16.08 at first follow-up and 16.46 at 3 months; REML mixed-effects modeling showed a significant timepoint effect (F (4, 34.55) = 9.15, p < 0.001), with significant Sidak-adjusted improvement at both timepoints. VAS pain showed no significant longitudinal effect. Conclusions: SSS for TSS appears feasible in a real-world, surgically diverse cohort including older and moderately frail patients. These findings support individualized SSS candidacy assessment.