Publications

INTRODUCTION: This study aimed to elucidate mechanisms underlying moyamoya disease (MMD) pathogenesis and to identify potential novel biomarkers. We utilized gene coexpression networks to identify hub genes associated with the disease.

METHODS: Twenty-one middle cerebral artery (MCA) samples from MMD patients and 11 MCA control samples were obtained from the Gene Expression Omnibus (GEO) dataset, GSE189993. To discover functional pathways and potential biomarkers, weighted gene coexpression network analysis (WGCNA) was employed. The hub genes identified were re-assessed through differential gene expression analysis (DGEA) via DESeq2 for further reliability verification. An additional 4 samples from the superficial temporal arteries (STA) from MMD patients were obtained from GSE141025 and a subgroup analysis stratified by arterial type (MCA vs. STA) DGEA was performed to assess if the hub genes associated with MMD are expressed significantly greater on the affected arteries compared to healthy ones in MMD.

RESULTS: WGCNA revealed a predominant module encompassing 139 hub genes, predominantly associated with the neuroactive ligand-receptor interaction (NLRI) pathway. Of those, 17 genes were validated as significantly differentially expressed. Neuromedin U receptor 1 (NMUR1) and thyrotropin-releasing hormone (TRH) were 2 out of the 17 hub genes involved in the NLRI pathway (log fold change [logFC]: 1.150, p = 0.00028; logFC: 1.146, p = 0.00115, respectively). MMD-only subgroup analysis stratified by location showed that NMUR1 is significantly overexpressed in the MCA compared to the STA (logFC: 1.962; p = 0.00053) which further suggests its possible localized involvement in the progressive stenosis seen in the cerebral arteries in MMD.

CONCLUSION: This is the first study to have performed WGCNA on samples directly affected by MMD. NMUR1 expression is well known to induce localized arterial smooth muscle constriction and recently, type 2 inflammation which can predispose to arterial stenosis potentially advancing the symptoms and progression of MMD. Further validation and functional studies are necessary to understand the precise role of NMUR1 upregulation in MMD and its potential implications.

BACKGROUND AND OBJECTIVES: The pipeline embolization device (PED) Flex with Shield technology is a third-generation flow diverter used for intracranial aneurysm treatment designed to decrease thrombogenicity through a phosphorylcholine coating. Herein, we aim to compare the rate of thromboembolic events in PED with Shield technology and PED without it through propensity score matching.

METHODS: We conducted a retrospective analysis of aneurysms treated with PED first-generation/PED Flex and PED with Shield between 2013 and 2023 at a single academic institution. Patients were matched through propensity score by controlling for confounding factors including age, smoking history, diabetes, previous subarachnoid hemorrhage, modified Rankin Scale pretreatment, location, aneurysm size, previous treatment, and clopidogrel or aspirin resistance. After matching, we evaluated for periprocedural and postoperative thromboembolic events. Data analysis was performed using Stata 14.

RESULTS: A total of 543 patients with 707 aneurysms treated in 605 procedures were included in the analysis. From these, 156 aneurysms were treated with PED with Shield (22.07%) and 551 (77.93%) without Shield technology. Propensity score matching resulted in 84 matched pairs. The rate of thromboembolic events was 3.57% for PED Shield and 10.71% for PED first-generation/PED Flex (P = .07), while retreatment rates were 2.38% for PED Shield and 8.32% for PED Flex (P = .09). Complete occlusion at first (P = .41) and last imaging follow-up (P = .71), in-stent stenosis (P = .95), hemorrhagic complications (P = .31), and functional outcomes (P = .66) were comparable for both groups.

CONCLUSION: This is the first study in the literature performing a propensity scored-matched analysis comparing PED with PED with Shield technology. Our study suggests a trend toward lower thromboembolic events for PED Shield, even after controlling for aspirin and clopidogrel resistance, and a trend toward lower aneurysm retreatment rates with PED Shield, without reaching statistical significance.

INTRODUCTION: Identifying predictors for rupture of small intracranial aneurysms (sIAs) have become a growing topic in the literature given the relative paucity of data on their natural history. The authors performed a meta-analysis to identify reliable predictors.

METHODS: PubMed, Scopus, and Web of Science were used to systematically extract references which involved at least 10 IAs <7mm which including a control group experiencing no rupture. All potential predictors reported in the literature were evaluated in the meta-analysis.

RESULTS: Fifteen studies yielding 4,739 sIAs were included in the meta-analysis. Four studies were prospective and 11 were retrospective. Univariate analysis identified 7 predictors which contradicted or are absent in the current scoring systems, while allowing to perform subgroup analysis for further reliability: patient age (MD -1.97, 95%CI -3.47-0.48; P = 0.01), the size ratio (MD 0.40, 95%CI 0.26-0.53; P < 0.00001), the aspect ratio (MD 0.16, 95%CI 0.11-0.22; P < 0.00001), bifurcation point (OR 3.76, 95%CI 2.41-5.85; P < 0.00001), irregularity (OR 2.95, 95%CI 1.91-4.55; P < 0.00001), the pressure loss coefficient (MD -0.32, 95%CI -0.52-0.11; P = 0.002), wall sheer stress (Pa) (MD -0.16, 95%CI -0.28-0.03; P = 0.01). All morphology related predictors listed above have been confirmed as independent predictors via multivariable analysis among the individual studies.

CONCLUSIONS: Morphology related predictors are superior to the classic patient demographic predictors present in most scoring systems. Given that morphology predictors take time to measure, our findings may be of great interest to developers seeking to incorporate artificial intelligence into the treatment decision-making process.

BACKGROUND AND OBJECTIVES: The choice of anesthesia type (general anesthesia [GA] vs nongeneral anesthesia [non-GA]) in middle meningeal artery embolization (MMAE) procedures for chronic subdural hematomas (cSDH) differs between institutions and left to care team discretion given lack of standard guidelines. We compare the outcomes of GA vs non-GA in MMAE.

METHODS: Consecutive patients receiving MMAE for cSDH at 14 North American centers (2018-2023) were included. Clinical, cSDH characteristics, and technical/clinical outcomes were compared between the GA/non-GA groups. Using propensity score matching (PSM), patients were matched controlling for age, baseline modified Rankin Scale, concurrent/prior surgery, hematoma thickness/midline shift, and baseline antiplatelet/anticoagulation. The primary end points included surgical rescue and radiographic success rates (≥50% reduction in maximum hematoma thickness with minimum 2 weeks of imaging). Secondary end points included technical feasibility, procedural complications, and functional outcomes.

RESULTS: Seven hundred seventy-eight patients (median age 73 years, 73.2% male patients) underwent 956 MMAE procedures, 667 (70.4%) were non-GA and 280 were GA (29.6%). After running 1:3 PSM algorithm, this resulted in 153 and 296 in the GA and non-GA groups, respectively. There were no baseline/procedural differences between the groups except radial access more significantly used in the non-GA group (P = .001). There was no difference between the groups in procedural technical feasibility, complications rate, length of stay, surgical rescue rates, or favorable functional outcome at the last follow-up. Subsequent 1:1 sensitivity PSM retained the same results. Bilateral MMAE procedures were more performed under non-GA group (75.8% vs 67.2%; P = .01); no differences were noted in clinical/radiographic outcomes between bilateral vs unilateral MMAE, except for longer procedure duration in the bilateral group (median 73 minutes [IQR 48.3-100] vs 54 minutes [39-75]; P < .0001). Another PSM analysis comparing GA vs non-GA in patients undergoing stand-alone MMAE retained similar associations.

CONCLUSION: We found no significant differences in radiological improvement/clinical outcomes between GA and non-GA for MMAE.

Percutaneous transluminal angioplasty (PTA) and stenting have been used for the treatment of internal carotid artery (ICA) stenosis over the past two decades. A systematic review was performed to understand the efficacy of PTA and/or stenting for petrous and cavernous ICA stenosis. In total, 151 patients (mean age 64.9) met criteria for analysis, 117 (77.5%%) were male and 34 (22.5%) were female. Of the 151 patients, 35 of them (23.2%) had PTA, and 116 (76.8%) had endovascular stenting. Twenty-two patients had periprocedural complications. There was no significant difference in the complication rates between the PTA (14.3%) and stent (14.7%) groups. Distal embolism was the most common periprocedural complication. Average clinical follow up for 146 patients was 27.3 months. Eleven patients (7.5%) out of 146 had retreatment. The treatment of petrous and cavernous ICA with PTA and stenting has relatively significant procedure related complication rates and adequate long-term patency.

BACKGROUND AND OBJECTIVES: The pipeline embolization device (PED) has become widely accepted as a safe and efficacious treatment for intracranial aneurysms with high rates of complete occlusion at initial follow-up. For aneurysms that are not completely occluded at initial follow-up, further treatment decision-making is varied. Furthermore, the risk of aneurysmal rupture in these incompletely occluded aneurysms after PED is not known. The objective of this study was to determine treatment decision-making that results in increased occlusion status at final follow-up and to evaluate risk of rupture in those aneurysms that do not go onto occlusion.

METHODS: This study is a retrospective review of prospective data for intracranial aneurysms treated with PED at two institutions from 2013 to 2019. Aneurysms with near-complete or incomplete occlusion at initial follow-up were included in the statistical analysis.

RESULTS: There were 606 total aneurysms treated at two academic institutions with PED with incomplete occlusion at initial follow-up in 134 aneurysms (22.1%). Of the 134 aneurysms that were nonoccluded at initial follow-up, 76 aneurysms (56.7%) went on to complete or near complete occlusion with final complete or near complete occlusion in 90.4% of all aneurysms treated. The time to final imaging follow-up was 28.2 months (13.8-44.3) Retreatment with a second flow diverter was used in 28 aneurysms (20.9%). No aneurysms that were incompletely occluded at initial follow-up had delayed rupture. Furthermore, older patient age was statistically significant for incomplete occlusion at initial follow-up ( P = .05).

CONCLUSION: Intracranial aneurysms treated with the PED that do not occlude at initial follow-up may go on to complete occlusion with continuous observation, alteration in antiplatelet regimens, or repeat treatment. Delayed aneurysmal rupture was not seen in patients with incomplete occlusion.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes.

OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya.

METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes.

RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563).

CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.

OBJECTIVE: Chronic subdural hematomas (CSDHs) are the among the most common conditions treated by neurosurgeons. Midline shift (MLS) is used as a radiological marker of CSDH severity and the potential need for urgent surgical evacuation. However, a patient's age may affect the degree of MLS for a given hematoma volume. This study aimed to investigate the correlation between the patient's age and the MLS caused by CSDH.

METHODS: The database of patients treated for CSDH was reviewed in a single institution. Patients with unilateral CSDH were included. To measure CSDH volume, the preprocedural head CT scans underwent 3D volumetric reconstruction using the TeraRecon software. The effect of age on MLS after adjusting for CSDH volume was investigated using linear regression analysis.

RESULTS: Sixty-nine hematomas in 69 patients were included. The age of patients ranged from 25 to 94 years (mean 71.6 years). Hematoma volume and MLS ranged from 27.8 to 215 mL (mean 99.3 mL) and 0-17 mm (mean 6.5 mm), respectively. On multivariate regression analysis, MLS showed a significant independent negative correlation with age after adjusting for CSDH volume (OR -0.11, 95% CI -0.16 to -0.06; p < 0.001), meaning that for a fixed CSDH volume, with each 10-year increase in age the MLS will reduce by 1.1 mm. Moreover, MLS-to-volume ratio showed a significant negative linear correlation with age (r2 = 0.32; p < 0.001). Ten-milliliter increments in CSDH volume resulted in a 1.09-mm increase in MLS in patients younger than 60 years, which is 2.4-fold higher compared to the 0.46-mm increase in those older than 75 years (p < 0.001).

CONCLUSIONS: For a fixed CSDH volume, older age correlates with significantly lower MLS. This could be explained by higher parenchymal compliance in older individuals due to increased brain atrophy, and a larger subdural space. Clinical use of MLS to estimate severity of CSDH and gauge treatment decisions should take the patient's age into account.

Most reported aneurysms concerning the middle meningeal artery (MMA) are pseudoaneurysms; however, there have been rare reports of non-traumatic MMA aneurysms in the literature. In this paper, we present the case of a 70-year-old female with a true 5-mm aneurysm in the anterior division of the left MMA that was causing erosion through the left temporal bone and was successfully treated with coil embolization. We also present a comprehensive literature review of non-traumatic MMA aneurysms reported since 1930. These aneurysms are associated with conditions such as hypertension, Paget's disease, and intracranial meningiomas and result from flow dynamics disturbances. Treatment involves both endovascular treatment and open surgery, while rupture, especially in the elderly, results in high disability, underscoring the importance of timely intervention upon identification.