Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6–9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

BACKGROUND: An angiogram-negative subarachnoid hemorrhage (SAH) with a high Hunt-Hess grade and atypical radiographic features warrants evaluation for occult lesions. Cervicomedullary spinal arteriovenous malformations (AVMs) are rare causes frequently missed on initial imaging. OBSERVATIONS: A 54-year-old male presented with a Hunt-Hess grade V SAH, and initial multimodal angiography findings were negative. Neurological status improved following external ventricular drain (EVD) placement. Imaging clues included a focal ventral cervicomedullary spot sign, disproportionate prepontine blood accumulation with inferior tracking, and an intraventricular hemorrhage. Angiography performed on day 10 revealed a 3-mm ruptured anterior spinal artery (ASA) aneurysm with cervicomedullary AVM. Endovascular treatment was high risk given the proximity of the ASA. Resection via far-lateral transcondylar approach was performed. Neuromonitoring demonstrated bilateral motor evoked potential (MEP) decline with preserved D-wave amplitude, prompting reinspection, revealing an inadvertent ASA trunk clipping, and enabling correction and complete MEP recovery. The lesion was obliterated without deficits. LESSONS: In a high-grade, angiogram-negative SAH, ventral blood distribution and spot signs should prompt targeted spinal angiography at 7–14 days. EVD placement can reverse herniation and coma in high-grade presentations. The far-lateral approach and cord rotation provide direct visualization for ventral spinal pathology when endovascular access is restricted. D-wave monitoring with transcranial MEPs enables real-time distinction between reversible ischemic changes and irreversible mechanical injury, guiding intraoperative decision-making. https://thejns.org/doi/10.3171/CASE26229

Nonroutine discharge (NRD), postoperative discharge to settings other than home, is an understudied quality metric vital to value-based health care systems. This study identified predictors of NRD after surgical treatment of unruptured intracranial aneurysms (UIAs). Demographic and clinical characteristics were obtained from the American College of Surgeons National Surgical Quality Improvement Program for patients with microsurgical treatment of UIAs from 2016 through 2020. The primary outcome was NRD. Propensity score matching and multivariable logistic regression were used to identify independent risk factors. Data from 929 patients were analyzed. NRD occurred in 158 (17%) of the patients. Factors associated with increased odds of NRD included age ≥65 years (odds ratio [OR] = 2.25), female sex (OR = 1.83), American Society of Anesthesiologists class≥III (OR = 2.07), diabetes mellitus (OR = 2.15), length of stay (LOS) ≥7 days (OR = 8.19), postoperative deep vein thrombosis (OR = 8.69), postoperative pneumonia (OR 5.89), and postoperative stroke (OR 6.98). Patients with vertebrobasilar UIAs had longer LOS than those with carotid UIAs (8.3 [8.9] vs. 6.2 [5.5] days; P = 0.03). Compared with simple UIAs, complex UIAs were associated with longer operative times (283 [116.9] vs. 228 [94.6] minutes; P < 0.001), longer LOS (6.0 [6.4] vs. 4.8 [4.0] days; P = 0.002), higher rates of postoperative stroke (8% vs. 4%; P = 0.01), and higher NRD rates (20% vs. 12%; P = 0.003). Demographic and perioperative factors were independently associated with NRD after UIA microsurgery. Identifying these predictors can improve risk stratification, optimize care pathways, and inform policies to enhance outcomes and reduce health care costs.

Nonroutine discharge (NRD) from the hospital carries considerable cost. We identified predictors of NRD after surgical treatment of ruptured intracranial aneurysms (IAs). The American College of Surgeons National Surgical Quality Improvement Program database was searched for patients with surgically treated ruptured IAs from 2016 through 2020. Demographics, clinical characteristics, preoperative comorbidities, procedural details, and 30-day morbidity and mortality were extracted. NRD risk factors were determined by multivariate logistic regression. Surgical outcomes and postoperative complications were compared by aneurysm complexity and location after propensity score matching. Among 671 patients, 277 (41%) had NRD, 591 (88%) underwent emergent surgery, and 466 (69%) had complex aneurysms. After matching, complex aneurysms were associated with higher frequencies of postoperative pneumonia (16% vs 10%, p=0.04), NRD (45% vs 32%, p=0.01), and 30-day reoperation (21% vs 13%, p=0.03). Aneurysms in the vertebrobasilar circulation were associated with a higher frequency of postoperative urinary tract infection (13% vs 5%, p=0.01) and organ/space surgical site infection (4% vs 0.7%, p=0.02). On multivariable analysis, NRD was associated with age ≥65 years (odds ratio [OR] 2.76), Black/African American (OR 1.86) or White (OR 2.16) race, preoperative immunosuppressive or steroid therapy (OR 4.46), complex aneurysms (OR 1.75), emergent surgery (OR 2.37), length of stay ≥21 days (OR 2.94), and postoperative pneumonia (OR 3.64) or sepsis (OR 5.64). Predictors of NRD after ruptured IA surgery included patient demographics, aneurysm characteristics, and postoperative complications. Early identification of high-risk patients and targeted discharge planning could reduce NRD rates.