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.

Extracranial-to-Intracranial Bypass for Distal Internal Carotid Artery and/or Proximal Middle Cerebral Artery Steno-Occlusive Disease: A Case Series of Clinical Outcomes at a Single, High-Volume Cerebrovascular Center.

BACKGROUND: Extracranial-to-intracranial (EC-IC) bypass was first described by Yasargil in the 1960s for treatment of symptomatic distal internal carotid artery (ICA) and/or proximal middle cerebral artery (MCA) steno-occlusive disease through direct anastomosis. Subsequent bypass trials failed to demonstrate benefit for overall outcomes and stroke rates compared with best medical therapy. However, the procedure remained in the neurosurgeon's armament, with studies showing benefits in select patient populations. With advancements in technology, patient selection has become more comprehensive. OBJECTIVE: To provide a contemporary evaluation of EC-IC bypass from our high-volume cerebrovascular center, focusing on associated clinical outcomes. METHODS: Consecutive patients who underwent direct EC-IC bypass surgeries for symptomatic distal ICA and/or proximal MCA steno-occlusive disease between April 2015 and September 2019 were identified retrospectively. Medical records were reviewed to collect demographics, clinical presentation, computed tomography perfusion imaging findings, transcranial Doppler results, procedure indication, donor vessel types, anastomosis site, bypass patency, periprocedural complications, postprocedural complications, symptom recrudescence, repeat or new interventions, subjective improvements, and modified Rankin Scale scores. RESULTS: We identified 27 patients who underwent 32 EC-IC bypass procedures. The rate of ipsilateral stroke was 9.4%, with a median follow-up of 8 months (IQR, 4-13 months). Patients experienced a 22.3% improvement in modified Rankin Scale scores, and 70.3% of patients reported subjective improvement and satisfaction at follow-up. CONCLUSION: Direct EC-IC bypass remains a viable option for revascularization in symptomatic patients with distal ICA and/or proximal MCA steno-occlusive disease.

Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching.

Impaired T cell immunity with aging increases mortality from infectious disease. The branching of Asparagine-linked glycans is a critical negative regulator of T cell immunity. Here we show that branching increases with age in females more than males, in naïve more than memory T cells, and in CD4+ more than CD8+ T cells. Female sex hormones and thymic output of naïve T cells (TN) decrease with age, however neither thymectomy nor ovariectomy altered branching. Interleukin-7 (IL-7) signaling was increased in old female more than male mouse TN cells, and triggered increased branching. N-acetylglucosamine, a rate-limiting metabolite for branching, increased with age in humans and synergized with IL-7 to raise branching. Reversing elevated branching rejuvenated T cell function and reduced severity of Salmonella infection in old female mice. These data suggest sex-dimorphic antagonistic pleiotropy, where IL-7 initially benefits immunity through TN maintenance but inhibits TN function by raising branching synergistically with age-dependent increases in N-acetylglucosamine.

Social Media Use Among Neurosurgery Trainees: A Survey of North American Training Programs.

BACKGROUND: Social media have revolutionized access to educational content. Given the extensive presence of social media, these platforms have the potential to influence neurosurgical training and education of residents and fellows. We explored the attitudes of neurosurgical trainees (postgraduate years 1-9) toward social media and their perceived influence on training and education. METHODS: This study was a survey of trainees at North American neurosurgery residency programs. A 22-item survey, including 2 free-text questions, was distributed through the Congress of Neurological Surgeons listserv. The survey consisted of questions regarding demographics, social media platform use, and trainee views on social media; their perceived impact on education and job performance was gauged using a 5-point Likert scale. Descriptive analysis was performed. RESULTS: The survey was disseminated to 1160 neurosurgery trainees, with a response rate of 15.3%. Of 178 respondents, 132 (74.2%) were men; 142 (79.8%) were 25-34 years old. All respondents used social media. The most commonly used platforms were Facebook (87.1%), followed by YouTube (84.3%), Instagram (81.5%), and Twitter (74.7%). The most common reasons for social media use were personal social (89.8%), networking (65.5%), and academic resources (65.0%); 113 respondents (63.5%) reported spending <25% of their time on social media for academics. The Neurosurgical Atlas (63.3%), Congress of Neurological Surgeons (11.2%), and American Association of Neurological Surgeons (10.1%) social media accounts were the most commonly used academic platforms. CONCLUSIONS: Social media use was ubiquitous among trainees. Although most used social media for personal social communication, most also used it for academic purposes.

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.

Is Endovascular Therapy for Stroke Cost-Effective Globally? A Systematic Review of the Literature.

OBJECTIVES: Cost-effectiveness of endovascular therapy (EVT) is a key consideration for broad use of this approach for emergent large vessel occlusion stroke. We evaluated the evidence on cost-effectiveness of EVT in comparison with best medical management from a global perspective. MATERIALS AND METHODS: This systematic review of studies published between January 2010 and May 2020 evaluated the cost effectiveness of EVT for patients with large vessel occlusion acute ischemic stroke. The gain in quality adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER), expressed as cost per QALY resulting from EVT, were recorded. The study setting (country, economic perspective), decision model, and data sources used in economic models of EVT cost-effectiveness were recorded. RESULTS: Twenty-five original studies from 12 different countries were included in our review. Five of these studies were reported from a societal perspective; 18 were reported from a healthcare system perspective. Two studies used real-world data. The time horizon varied from 1 year to a lifetime; however, 18 studies reported a time horizon of >10 years. Twenty studies reported using outcome data from randomized, controlled clinical trials for their models. Nineteen studies reported using a Markov model. Incremental QALYs ranged from 0.09-3.5. All studies but 1 reported that EVT was cost-effective. CONCLUSIONS: Evidence from different countries and economic perspectives suggests that EVT for stroke treatment is cost-effective. Most cost-effectiveness studies are based on outcome data from randomized clinical trials. However, there is a need to study the cost-effectiveness of EVT based solely on real-world outcome data.

Transradial access for flow diversion of intracranial aneurysms: Case series.

BACKGROUND: Transradial access for neurointerventions offers advantages of fewer access-site complications, reduced procedure time, and greater patient comfort over transfemoral access. Data about transradial access for flow diversion are limited. We share our early experience with transradial access for flow diversion in a relatively large case series. METHODS: Consecutive patients who underwent Pipeline embolization device (Medtronic) deployment via transradial access were included in the study, irrespective of location and laterality of the intracranial aneurysm. The cases were performed between July 2016 and October 2019. Demographics, aneurysm characteristics, and procedure-related details (including catheter systems used) were recorded and statistically evaluated. RESULTS: Thirty-five transradial flow diversion procedures were attempted in 32 patients, of which 33 procedures were successful. In two cases involving left common carotid artery and internal carotid artery access, guide catheter herniation into the aortic arch led to abandonment of transradial access in favor of transfemoral access. The most common aneurysm locations in the transradial access procedures were the posterior communicating artery (n = 7), ophthalmic artery (n = 7), and superior hypophyseal artery (n = 7). Most transradial access procedures (66.7%) were performed using a biaxial catheter system. 6-French Benchmark (Penumbra) and Phenom 27 (Medtronic) were the most commonly utilized guide- and microcatheters, respectively. One patient had intraprocedural subarachnoid hemorrhage. No access-site complications occurred. CONCLUSION: This study demonstrates safety and feasibility of transradial access for Pipeline embolization device deployment and shows the versatility of this approach for different catheter systems. Tortuosity and acute angulation of the left common carotid artery and internal carotid artery were associated with approach failure.

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.

Size of ruptured intracranial aneurysms: a systematic review and meta-analysis.

BACKGROUND: There is wide variation in the reported size of ruptured intracranial aneurysms and methods of size estimation. There is widespread belief that small aneurysms < 7 mm do not rupture. Therefore, we performed a systematic review and meta-analysis of the literature to determine the size of ruptured aneurysms according to aneurysm locations and methods of size estimation. METHODS: We searched PubMed, Cochrane, CINAHL, and EMBASE databases using a combination of Medical Subject Headings (MeSH) terms. We included articles that reported mean aneurysm size in consecutive series of ruptured intracranial. We excluded studies limited to a specific aneurysm location or type. The random-effects model was used to calculate overall mean size and location-specific mean size. We performed meta-regression to explain observed heterogeneity and variation in reported size. RESULTS: The systematic review included 36 studies and 12,609 ruptured intracranial aneurysms. Overall mean aneurysm size was 7.0 mm (95% confidence interval [CI 6.2-7.4]). Pooled mean size varied with location. Overall mean size of 2145 ruptured anterior circulation aneurysms was 6.0 mm (95% CI 5.6-6.4, residual I2 = 86%). Overall mean size of 743 ruptured posterior circulation aneurysms was 6.2 mm (95% CI 5.3-7.0, residual I2 = 93%). Meta-regression identified aneurysm location and definition of size (i.e., maximum dimension vs. aneurysm height) as significant determinants of aneurysm size reported in the studies. CONCLUSIONS: The mean size of ruptured aneurysms in most studies was approximately 7 mm. The general wisdom that aneurysms of this size do not rupture is incorrect. Location and size definition were significant determinants of aneurysm size.

Rapid temporary coiling of the parent artery for the management of intraprocedural aneurysm rupture.

Intraprocedural rupture (IPR) of an intracranial aneurysm is the most feared complication of primary and stent-assisted coiling because it carries a high risk of morbidity and mortality. The endovascular strategy applied to control IPR depends on the cause of the rupture and stage of the procedure. Rupture during primary or stent-assisted coiling is traditionally managed with the use of continued packing, balloon microcatheter placement, or in rare cases, with parent artery sacrifice. In this technical note, we describe the use of temporary coiling of the parent artery to control IPR in three cases. Temporary parent artery coiling creates a subocclusive state, resulting in aneurysmal blood flow reduction without interruption of blood flow to the distal territory. Flow reduction combined with the thrombogenicity of the previously deployed coils results in hemostasis. In the cases presented here, IPR occurred during the late stage of coiling. In each case, parent artery coiling was performed along with heparin reversal. After confirmation of hemostasis, the coils were retrieved to restore normal blood flow. We demonstrate that the technique of temporary parent artery coiling may be a safe and effective option for the management of IPR during primary or stent-assisted coiling.

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.

One and done? The effect of number of Pipeline embolization devices on aneurysm treatment outcomes.

BACKGROUND: Controversy exists regarding the optimum number of flow diverters for the treatment of intracranial aneurysms. We explored the effect of the number of Pipeline embolization devices (PEDs; Medtronic, Dublin, Ireland) deployed on rates of aneurysm occlusion and complications. METHODS: Consecutive patients who underwent saccular intracranial aneurysm treatment solely with the PED were included in this retrospective study. Computed tomographic, magnetic resonance, or digital subtraction angiographic images at 6 and 12 months and last follow-up (>12 months) were reviewed for aneurysm occlusion. Complication and retreatment rates were recorded and analyzed statistically. RESULTS: The study included 141 aneurysm treatments in 119 patients. A single PED was deployed in 105 cases, two PEDs in 31 cases, and three PEDs in 5 cases (total = 182 devices). Six-month angiographic data were available for 103 patients. Occlusion rates were 67.1% for single-PED cases and 90.0% for cases with > 1 PED (p = 0.028). The 12-month occlusion rate (follow-up available for 132) for single-PED cases was 74.7% compared to 91.7% for multiple-PED cases (p = 0.04). On multivariate analysis, number of PEDs was an independent predictor of aneurysm occlusion at 12 months (odds ratio 6.3, 95% confidence interval 1.8-22.8, p = 0.005). Thromboembolic complication rates were the same in the single- and multiple-PED treatment groups (2.8%). The retreatment rate was higher in patients treated with a single PED (16.2% vs. 0%, p = 0.01). CONCLUSIONS: Deployment of > 1 Pipeline embolization device was associated with higher intracranial aneurysm occlusion and lower retreatment rates. No significant difference was found in complication rates.

Large Vessel Occlusion in Acute Ischemic Stroke Patients: A Dual-Center Estimate Based on a Broad Definition of Occlusion Site.

BACKGROUND: Accurate assessment of the frequency of large vessel occlusion (LVO) is important to determine needs for neurointerventionists and thrombectomy-capable stroke facilities. Current estimates vary from 13% to 52%, depending on acute ischemic stroke (AIS) definition and methods for AIS and LVO determination. We sought to estimate LVO prevalence among confirmed and suspected AIS patients at 2 comprehensive US stroke centers using a broad occlusion site definition: internal carotid artery (ICA), first and second segments of the middle cerebral artery (MCA M1,M2), the anterior cerebral artery, vertebral artery, basilar artery, or the proximal posterior cerebral artery. METHODS: We analyzed prospectively maintained stroke databases of patients presenting to the centers between January and December 2017. ICD-10 coding was used to determine the number of patients discharged with an AIS diagnosis. Computed tomography angiography (CTA) or magnetic resonance angiography (MRA) was reviewed to determine LVO presence and site. Percentages of patients with LVO among the confirmed AIS population were reported. RESULTS: Among 2245 patients with an AIS discharge diagnosis, 418 (18.6%:95% confidence interval [CI] 17.3%-20.0%) had LVO documented on CTA or MRA. Most common occlusion site was M1 (n=139 [33.3%]), followed by M2 (n=114 [27.3%]), ICA (n=69[16.5%]), and tandem ICA-MCA lesions (n=44 [10.5%]). Presentation National Institutes of Health Stroke Scale scores were significantly different for different occlusion sites (P=.02). CONCLUSIONS: The LVO prevalence in our large series of consecutive AIS patients was 18.6% (95% CI 17.3%-20.0%). Despite the use of a broad definition, this estimate is less than that reported in most previous studies.

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.

The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states.

Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that the long non-coding RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 is dynamically regulated by neuronal activity in vitro and in vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 and KCNIP1, and induces a neuronal hyper-potentiation phenotype in iPSC-derived human cortical neurons following antisense oligonucleotide knockdown. Next generation sequencing reveals a strong association of NEAT1 with increased ion channel gene expression upon activation of iPSC-derived neurons following NEAT1 knockdown. Furthermore, we show that while NEAT1 is acutely down-regulated in response to neuronal activity, repeated stimulation results in NEAT1 becoming chronically unresponsive in independent in vivo rat model systems relevant to temporal lobe epilepsy. We extended previous studies showing increased NEAT1 expression in resected cortical tissue from high spiking regions of patients suffering from intractable seizures. Our results indicate a role for NEAT1 in modulating human neuronal activity and suggest a novel mechanistic link between an activity-dependent long non-coding RNA and epilepsy.

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.