Originally identified as a potential receptor for opioids, the sigma-1 receptor is now recognized as an intracellular chaperone protein associated with mitochondria-associated membranes at the endoplasmic reticulum (ER). Over the past two decades, extensive research has revealed that the sigma-1 receptor regulates many cellular processes, such as calcium homeostasis, oxidative stress responses, protein folding, and mitochondrial function. The various functions of the sigma-1 receptor highlight its role as a central modulator of neuronal health and may be a promising pharmacological target across multiple neurodegenerative conditions. Herein, we provide an overview of the current pharmacological understanding of the sigma-1 receptor with an emphasis on the signaling mechanisms involved. We examine its pathological implications in common neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. We then highlight how sigma-1 receptor modulation may influence disease progression as well as potential pharmacological mechanisms to alter disease outcomes. The translational potential of sigma-1 receptor therapies is discussed, as well as the most up-to-date results of ongoing clinical trials. This review aims to clarify the therapeutic potential of the sigma-1 receptor in neurodegeneration and guide future research in these diseases.

Originally identified as a potential receptor for opioids, sigma-1 receptor is a class of intracellular receptors expressed in various tissues including neurons. As a resident protein in the mitochondria-associated endoplasmic reticulum (ER) membrane, sigma-1 receptor has been found involved in various biological and disease processes including stress responses, neurotransmission, and neurodegenerative diseases. Herein we discuss the history, structure, functions, and pharmacology of sigma-1 receptor and its pathological implications in neurodegenerative diseases.

The formation and progression of intracranial aneurysms are influenced by multiple factors. Previous studies have shown the local geometry surrounding an aneurysm to influence its development. The geometry of the global cerebral vasculature, however, and its potential effects on aneurysms have not been well elucidated. We hypothesized that select geometries within the anterior cerebral circulation would differ among those with ruptured and unruptured aneurysms. We conducted a retrospective analysis of 38 patients who presented to our institution for catheter-based 3D rotational cerebral angiography for assessment of intracranial aneurysms. Geometric analysis was conducted using Materialise Mimics and 3-Matic. Those with a ruptured aneurysm (n = 7) had a significantly larger bifurcation angle between the anterior cerebral artery (ACA) and middle cerebral artery (MCA) compared to patients with unruptured aneurysms (97.96°, 91.60°, P = 0.01). Subgroup analysis demonstrated larger ACA diameters in the cohort of patients with ACA aneurysms (3.14 mm) compared to those with internal carotid artery (ICA) and MCA aneurysms (2.45 mm, 2.61 mm, P = 0.004). Patients over the age of 65 had larger MCA bifurcation angles (94.87°) compared to their younger counterparts (86.58°, P = 0.024). Males exhibited a significantly larger petrous ICA diameter (5.33 mm vs. 4.53 mm, P < 0.001), ICA genu diameter (4.97 mm vs. 4.43 mm, P = 0.017), and ACA diameter (2.96 mm vs. 2.55 mm, P = 0.010), compared to female patients, but a smaller ACA-MCA bifurcation angle (91.11° vs. 94.31°, P = 0.039). We conclude that geometric differences may be the result of systemic vascular remodeling and a potential indicator of aneurysm integrity.

Undifferentiated pleomorphic sarcoma (UPS) is a rare and aggressive soft tissue tumor of unknown histogenesis. UPS most often arises in the extremities or trunk, where wide surgical excision is feasible. Rarely, UPS involves the intracranial space, where critical structures may inhibit complete resection. Given its rarity and historical misclassification as malignant fibrous histiocytoma (MFH), knowledge of intracranial UPS is limited, and there are no clear treatment guidelines. We systematically reviewed all available cases of intracranial UPS to consolidate existing literature and assess prognosis and management considerations. A systematic review was conducted according to PRISMA guidelines. PubMed and Embase were searched for reports of intracranial UPS or storiform-pleomorphic MFH. Eligible studies included at least one histologically confirmed case treated with surgery, chemotherapy, or radiotherapy and reported outcomes. Data on demographics, tumor location, treatment, follow-up, and survival were extracted. Event-free survival (EFS) and overall survival (OS) were analyzed by treatment modality, age, sex, and tumor location using Kaplan-Meier and log-rank tests. From 801 records, 40 studies with 48 patients were included. The median age was 45 years, and 50% were female. 15% had prior radiotherapy. Most tumors were extra-axial (45%) and nearly all patients underwent surgery, with 82.1% achieving gross total resection. Median EFS and OS were 18 and 24 months, respectively. No survival differences were seen by treatment modality, age, or sex. Overall survival was longer for extra-axial tumors compared to intra-axial or skull base tumors ( p = 0.016). Intracranial UPS is a rare and aggressive tumor, with worse prognosis compared to those that are extracranial. Among factors that we evaluated, extra-axial location was the strongest positive prognostic factor. Surgical resection with adjuvant chemoradiation showed the longest median survival. Ongoing case reports are required to refine management guidelines and improve patient outcomes.

Background/Objectives: Preoperative antithrombotic therapy is common among patients undergoing subdural hematoma (SDH) evacuation. However, the association with postoperative outcomes remains uncertain. We evaluated this potential association using a multicenter electronic health record cohort and a single-center cohort. Methods: We performed a retrospective cohort study using TriNetX, a multicenter electronic health record (EHR) database, and a single-center cohort. TriNetX was used to identify adults undergoing evacuation of nontraumatic subdural hematoma between 2005 and 2025. The exposed cohort was defined as documented oral anticoagulant or antiplatelet exposure within 7 days before surgery, after which patients were propensity-score matched 1:1. The single-center cohort included surgically treated subdural hematoma patients with clinical, radiographic, laboratory, and operative data. Postoperative outcomes included 30-day mortality, short-term thrombotic complications, and 90-day repeat subdural hematoma surgery. Results: In TriNetX, 15,651 eligible patients were identified. Matched cohorts included 1455 exposed and 1455 unexposed patients. Preoperative antithrombotic exposure was associated with higher 90-day repeat surgery (9.7% vs. 6.5%; hazard ratio [HR] 1.52; p = 0.001), whereas 30-day mortality and 14-day thrombotic complications did not differ significantly. The single-center cohort included 164 surgically treated patients, including 103 exposed and 61 unexposed patients. The reoperation association was not reproduced. However, exposed patients had higher unadjusted 30-day and overall mortality that attenuated after multivariable Cox adjustment. Conclusions: Preoperative antithrombotic exposure was associated with repeat surgery in the TriNetX cohort but not in the single-center cohort. Together, these findings suggest that antithrombotic exposure may identify a medically complex surgical SDH population requiring individualized postoperative surveillance.

Background: Delta large-channel endoscopic decompression is an emerging, minimally invasive approach for lumbar degenerative disease, but its comparative effectiveness and perioperative performance have not been comprehensively synthesized. We performed a systematic review and meta-analysis to evaluate clinical, functional, and safety outcomes of Delta large-channel endoscopy relative to established decompression techniques. Methods: PubMed, Embase, and Scopus were searched from database inception through July 2025 (PROSPERO #CRD420251107750). Peer-reviewed English-language studies reporting extractable outcomes after Delta large-channel endoscopic surgery in adults were included. Random-effects meta-analyses were used for pooled comparisons. Results: Nine studies met the inclusion criteria, comprising 737 patients overall, including 379 treated with Delta large-channel endoscopy and 358 treated with comparator procedures. Reported outcome assessment generally ranged from 1 week to 12 months postoperatively, or variable latest follow-up timepoints, and mean follow-up was inconsistently reported. All studies originated in China and included five retrospective cohorts, two randomized controlled trials, one prospective cohort, and one case series. The pooled mean operative time for Delta procedures was 88.28 min (95% CI, 79.24–97.31), pooled mean intraoperative blood loss was 24.58 mL (95% CI, 11.14–38.02), and pooled mean hospital stay was 4.59 days (95% CI, 2.87–6.31). Compared with microscopic, endoscopic, and open techniques, Delta large-channel endoscopy showed no statistically significant differences in operative time (MD = 6.95 min, 95% CI: −11.51–25.40 min; p = 0.4037), intraoperative blood loss (MD, −40.62 mL; 95% CI, −83.68–2.44; p = 0.0598), 3-month ODI change from baseline (MD, 1.26; 95% CI, −2.17–4.69; p = 0.3661), or complication rates (OR, 0.67; 95% CI, 0.40–1.12; p = 0.1094). Delta procedures were associated with shorter hospital stay (MD, −1.69 days; 95% CI, −2.83 to −0.56; p = 0.0122) and marginally greater improvement in six-month VAS low back pain change from baseline (MD, 0.28; 95% CI, 0.26–0.29; p = 0.0002), though clinically insignificant. The pooled complication rate for Delta procedures was 6.0% (95% CI, 4–10%) and reported rates of excellent or good MacNab outcomes ranged from 80 to 93% across Delta cohorts. Conclusions: Delta large-channel endoscopy may provide clinical and functional outcomes comparable to established decompression techniques, with similar safety and potential perioperative benefits, including shorter hospitalization. However, these findings are based on limited, low-certainty evidence with high heterogeneity and should be interpreted as exploratory rather than definitive. Additional multicenter studies with longer follow-up, broader geographic representation, and higher methodological quality are necessary before definitive conclusions regarding comparative effectiveness can be established.