Spinal Meningiomas: A Comprehensive Review and Update on Advancements in Molecular Characterization, Diagnostics, Surgical Approach and Technology, and Alternative Therapies.

Spinal meningiomas are the most common intradural, extramedullary tumor in adults, yet the least common entity when accounting for all meningiomas spanning the neuraxis. While traditionally considered a benign recapitulation of their intracranial counterpart, a paucity of knowledge exists regarding the differences between meningiomas arising from these two anatomic compartments in terms of histopathologic subtypes, molecular tumor biology, surgical principles, long-term functional outcomes, and recurrence rates. To date, advancements at the bench have largely been made for intracranial meningiomas, including the discovery of novel gene targets, DNA methylation profiles, integrated diagnoses, and alternative systemic therapies, with few exceptions reserved for spinal pathology. Likewise, evolving clinical research offers significant updates to our understanding of guiding surgical principles, intraoperative technology, and perioperative patient management for intracranial meningiomas. Nonetheless, spinal meningiomas are predominantly relegated to studies considering non-specific intradural extramedullary spinal tumors of all histopathologic types. The aim of this review is to comprehensively report updates in both basic science and clinical research regarding intraspinal meningiomas and to provide illustrative case examples thereof, thereby lending a better understanding of this heterogenous class of central nervous system tumors.

Preradiosurgical Embolization of Arteriovenous Malformations Reduces Target Volume - The Main Determinant for Complete Obliteration.

BACKGROUND: Embolization and stereotactic radiosurgery (SRS) have increasingly been used to treat complex arteriovenous malformations (AVMs). We studied outcomes of AVM patients treated through a multidisciplinary approach, examined the effect of embolization on SRS success, and analyzed predictors of treatment failure. METHODS: We retrospectively reviewed a prospectively maintained database of patients with AVMs treated with Gamma Knife (Leksell) SRS over an 11-year period. Patients with incomplete medical records and follow-up <2 years were excluded. Demographics, clinical presentation, previous rupture history, angiographic nidus size, Spetzler-Martin (S-M) grade, adjunctive endovascular embolization and microsurgical resection, radiologic evidence of obliteration and hemorrhage, and clinical outcomes (modified Rankin Scale [mRS] scores) were recorded. Radiosurgery-related details including nidus volume and number of sessions and radiosurgery-, embolization-, and resection-associated complications were also recorded. RESULTS: Eighty-three patients (mean age, 41.0 ± 21.3 years) were included. Mean reduction in AVM nidus target volume with endovascular embolization was 66.0 ± 19.7%. S-M grade reduction was achieved in 51.6% cases. Total obliteration after SRS was achieved in 56 AVMs (67.5%) after 2 years, and in 38 (86.4%) after 4 years. Two (2.4%) patients had rehemorrhage after SRS. Overall complication rate was 3.6%. Median angiographic follow-up was 55.5 months. Favorable outcomes (mRS = 0-2) were seen in 77.1%. SRS target volume was an independent predictor of treatment failure regardless of pre-SRS embolization. CONCLUSIONS: High AVM obliteration rates were achieved with judicious use of radiosurgery alone or with embolization. Embolization reduced target nidus volume by an average of 66%. SRS target volume was an independent predictor of treatment failure.

Systematic Review of WHO Grade 4 Astrocytoma in the Cerebellopontine Angle: The Impact of Anatomic Corridor on Treatment Options and Outcomes.

Background Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an illustrative case and systematic review of rare, predominantly extra-axial World Health Organization (WHO) grade 4 astrocytomas located within the cerebellopontine angle (CPA) and explore the impact of anatomic location on diagnosis, management, and outcomes. Methods A systematic review of adult patients with predominantly extra-axial WHO grade 4 CPA astrocytomas was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through December 2022. Results Eighteen articles were included comprising 21 astrocytomas: 13 exophytic tumors arising from the cerebellopontine parenchyma and 8 tumors originating from a cranial nerve root entry zone. The median OS was 15 months with one-third of cases demonstrating delayed diagnosis. Gross total resection, molecular genetic profiling, and use of ancillary treatment were low. We report the only patient with an integrated isocitrate dehydrogenase 1 (IDH-1) mutant diagnosis, who, after subtotal resection and chemoradiation, remains alive at 40 months without progression. Conclusion The deep conical-shaped corridor and abundance of eloquent tissue of the CPA significantly limits both surgical resection and utility of device-based therapies in this region. Prompt diagnosis, molecular characterization, and systemic therapeutic advances serve as the predominant means to optimize survival for patients with rare skull base astrocytomas.

Comparison of Minimally Invasive Total versus Subtotal Resection of Spinal Tumors: A Systematic Review and Meta-Analysis.

OBJECTIVE: With the advent of minimally invasive techniques, minimally invasive spine surgery (MISS) has become a realistic option for many spine cases. This study aims to evaluate the operative and clinical outcomes of MISS for total versus subtotal tumor resection from current evidence. METHODS: A literature search was performed using the search term (Minimally invasive surgery OR MIS) AND (spine tumor OR spinal tumor). Studies including both minimally invasive total and subtotal resection cases with operative or clinical data were included. RESULTS: Seven studies describing 159 spinal tumor cases were included. Compared with total resection, subtotal resection showed no significant differences in surgical time (mean difference (MD), 9.44 minutes; 95% confidence interval [CI], -47.66 to 66.55 minutes; P = 0.37), surgical blood loss (MD, -84.72 mL; 95% CI, -342.82 to 173.39 mL; P = 0.34), length of stay (MD, 1.38 days; 95% CI, -0.95 to 3.71 days; P = 0.17), and complication rate (odds ratio, 9.47; 95% CI, 0.34-263.56; P = 0.12). Pooled analyses with the random-effects model showed that neurologic function improved in 89% of patients undergoing total resection, whereas neurologic function improved in 61% of patients undergoing subtotal resection. CONCLUSIONS: Our analyses show that there is no significant difference in operative outcomes between total and subtotal resection. Patients undergoing total resection showed slightly better improvement in neurologic outcomes compared with patients undergoing subtotal resection. Overall, this study suggests that both total and subtotal resection may result in comparable outcomes for patients with spinal tumors. However, maximal safe resection remains the ideal treatment because it provides the greatest chance of long-term benefit.

A novel combination therapy targeting ubiquitin-specific protease 5 in MYCN-driven neuroblastoma.

Histone deacetylase (HDAC) inhibitors are effective in MYCN-driven cancers, because of a unique need for HDAC recruitment by the MYCN oncogenic signal. However, HDAC inhibitors are much more effective in combination with other anti-cancer agents. To identify novel compounds which act synergistically with HDAC inhibitor, such as suberanoyl hydroxamic acid (SAHA), we performed a cell-based, high-throughput drug screen of 10,560 small molecule compounds from a drug-like diversity library and identified a small molecule compound (SE486-11) which synergistically enhanced the cytotoxic effects of SAHA. Effects of drug combinations on cell viability, proliferation, apoptosis and colony forming were assessed in a panel of neuroblastoma cell lines. Treatment with SAHA and SE486-11 increased MYCN ubiquitination and degradation, and markedly inhibited tumorigenesis in neuroblastoma xenografts, and, MYCN transgenic zebrafish and mice. The combination reduced ubiquitin-specific protease 5 (USP5) levels and increased unanchored polyubiquitin chains. Overexpression of USP5 rescued neuroblastoma cells from the cytopathic effects of the combination and reduced unanchored polyubiquitin, suggesting USP5 is a therapeutic target of the combination. SAHA and SE486-11 directly bound to USP5 and the drug combination exhibited a 100-fold higher binding to USP5 than individual drugs alone in microscale thermophoresis assays. MYCN bound to the USP5 promoter and induced USP5 gene expression suggesting that USP5 and MYCN expression created a forward positive feedback loop in neuroblastoma cells. Thus, USP5 acts as an oncogenic cofactor with MYCN in neuroblastoma and the novel combination of HDAC inhibitor with SE486-11 represents a novel therapeutic approach for the treatment of MYCN-driven neuroblastoma.

Transradial middle meningeal artery embolization for chronic subdural hematoma using Onyx: case series.

BACKGROUND: Middle meningeal artery (MMA) embolization is an emerging therapy for the resolution of subacute or chronic subdural hematoma (CSDH). CSDH patients are often elderly and have several comorbidities. We evaluated our experience with transradial access (TRA) for MMA embolization using predominantly Onyx under conscious sedation. METHODS: Data for consecutive patients who underwent transradial MMA embolization for CSDH during a 2-year period (2018-2019) were analyzed from a single-center, prospectively-maintained database. Patient demographics, comorbidities, ambulatory times, subdural hematoma resorption status, and guide catheter type were recorded. Conversion to femoral access and complication rates were also recorded. Univariate and multivariate analyses were performed. RESULTS: Forty-six patients (mean age, 71.7±14.4 years) were included in this study. Mean CSDH size was 14±5.5 mm. Most (91.3%) TRA embolizations were performed with 6-French 0.071-inch Benchmark guide catheters (Penumbra). MMA embolization was successful in 44 patients (95.7%) (including two cases of TRA conversion). Twenty-one (48%) patients had a severe Charlson Comorbidity Index (>5). Symptomatic improvement was noted in 39 of 44 patients (88.6%). Mean length of stay was 4±3 days. Patients were ambulated immediately postprocedure. At mean follow-up (8±4 weeks), 86.4% of patients had complete or partial CSDH resolution. Persistent use of antiplatelet agents after the procedure was associated with failed or minimal CSDH resorption (5 of 6, 83.3% vs 9 of 38 23.7% with complete or near-complete resolution; P=0.009). CONCLUSION: Transradial Onyx MMA embolization under conscious sedation is safe and effective for CSDH treatment. TRA may be especially useful in elderly patients with numerous comorbidities.

Is Contrast Stasis After Pipeline Embolization Device Deployment Associated with Higher Aneurysm Occlusion Rates?

OBJECTIVE: To assess the association of degree of contrast stasis in intracranial aneurysms (IAs) immediately after Pipeline embolization device (PED; Medtronic, Dublin, Ireland) deployment with 6- and 12-month angiographic occlusion rates. METHODS: This retrospective cohort study included consecutive patients undergoing PED deployment for saccular IA treatment at a large-volume cerebrovascular center over a 4-year 9-month period. Angiographic images obtained immediately after PED deployment were graded according to amount of intra-aneurysmal contrast flow during the late venous phase: 0 = no stasis; 1 = <50% contrast stasis; 2 = 50%-75% stasis; and 3 = >75%-99% stasis. Follow-up occlusion rates were determined by digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography. RESULTS: The study included 119 patients in whom 182 PEDs were deployed to treat 141 aneurysms. A single PED was deployed in 105 (74.5%) aneurysms. The internal carotid artery was the commonest aneurysm site (119 [85%]). Fifty-two (36.9%) aneurysms were grade 0; 33 (23.4%) were grade 1; 46 (32.6%) were grade 2; and 10 (7.1%) were grade 3 immediately post-treatment. A 6-month follow-up angiogram available for 101 aneurysms showed complete occlusion (no flow into the aneurysm) in 74 (73.3%) aneurysms. A 12-month follow-up study available for 132 aneurysms showed complete occlusion in 79.5%. At last follow-up, occlusion rates were not significantly different for different contrast stasis grades (P = 0.60). Mean angiographic follow up for all IAs was 23v±v17.7 months. IA size, sex, age, and smoking were not significant predictors of occlusion. CONCLUSIONS: The degree of aneurysm contrast stasis immediately after PED deployment is not statistically associated with 6- and 12-month angiographic occlusion rates.

Adar3 Is Involved in Learning and Memory in Mice.

The amount of regulatory RNA encoded in the genome and the extent of RNA editing by the post-transcriptional deamination of adenosine to inosine (A-I) have increased with developmental complexity and may be an important factor in the cognitive evolution of animals. The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown. Meta-analysis of published data indicates that mouse Adar3 expression is highest in the hippocampus, thalamus, amygdala, and olfactory region. Consistent with this, we show that mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice. We also show that ADAR3 transiently translocates from the cytoplasm to the nucleus upon KCl-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals.

Tuberculous dactylitis.

Tuberculous dactylitis is a rare condition and a diagnostic challenge. Tissue biopsies can be negative for microscopy and culture. Polymerase chain reaction and DNA probes for mycobacterium tuberculosis can provide an earlier diagnosis. Surgery and antimicrobial therapy remain the mainstay of management.