Predictors of angiographic resolution in patients with presumed reversible cerebral vasoconstriction syndrome.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome is a complex neurovascular syndrome that presents with varying neurological deficits as well as segmental vasoconstriction of the small and medium cerebral arteries. There is limited literature on pathologies that mimic reversible cerebral vasoconstriction syndrome, so this study aims to understand what factors may impact the angiographic confirmation of reversible cerebral vasoconstriction syndrome on follow-up and play a role in establishing the diagnosis. METHODS: The Clinical Research Data Warehouse at this institution was employed to search the medical records for patients with diagnosis and treatment of reversible cerebral vasoconstriction syndrome between January 2010 and May 2021. After screening, 32 patients met the inclusion criteria for a presumed diagnosis of reversible cerebral vasoconstriction syndrome with both angiography on presentation and at three-month follow-up after treatment. Patients were divided into two categories: those with complete angiographic resolution, versus partial or no improvement on follow-up. Clinical and radiographic data were analyzed. RESULTS: Patients who had partial or no resolution were more likely to have a history of hypertension (p = 0.001), higher systolic blood pressure on admission (p = 0.047), and present with a recurrent thunderclap headache (p = 0.038). Binary logistic regression selected for hypertension (odds ratio [OR] 18.35 [95% CI, 1.37-245.1]) as predictive of not having reversible cerebral vasoconstriction syndrome, as can be seen by partial or no resolution on follow-up angiography (p = 0.028). CONCLUSION: Complete resolution on follow-up angiography is a distinguishing factor of reversible cerebral vasoconstriction syndrome. Our analysis revealed that a history of hypertension is the most significant predictor of confirming that a patient may not have reversible cerebral vasoconstriction syndrome. This is due, in part, to increased atherosclerotic or hypertensive cerebral arterial changes, which can mimic reversible cerebral vasoconstriction syndrome and present as partial or no resolution on angiography.

Refinement of nBCA embolization technique in treatment of metastatic spinal tumors: Case series and technical report.

BACKGROUND AND OBJECTIVES: Preoperative embolization of metastatic spinal tumors (MSTs) has proven advantageous in limiting intraoperative blood loss (IBL) during resection. N-butyl cyanoacrylate (nBCA) is a liquid embolic agent known for its rapid hemostatic effects. However, nBCA is associated with a higher risk of distal nontarget embolization. This study highlights the refinement of the embolization technique and assesses its efficacy in performing an initial distal segmental artery plug with concentrated nBCA followed by proximal diluted nBCA for MSTs. METHODS: A retrospective review of patients with MST (2018-2023) was performed. Patients who underwent preoperative nBCA endovascular embolization prior to tumor resection and spinal instrumentation were included. Baseline standard spinal angiography was performed. RESULTS: Sixteen patients (13 men, 3 women; 56.0 ± 12.4 years) met inclusion criteria. And 43.75% (7 of 16) had thoracic levels, 37.5% (6 of 16) lumbar, and 18.75% (3 of 16) sacral. The most common primary tumor was renal cell carcinoma (43.75%, 7 of 16). A total of 43 pedicles were embolized (median 3), resulting in complete/near complete obliteration of the tumor blush. Most pedicles (83.7%, 36 of 43) received a single dilute concentration of nBCA; however, 16.3% (7 of 43) received two separate concentrations of nBCA, a denser concentration distally into the segmental artery and a diluted concentration proximally into the tumor bed. Mean IBL was 1150 ± 1201 mL in 3 distal plug patients distal plug patients versus 1625 ± 681 mL in 12 other patients. There were no complications related to embolization. CONCLUSION: Performing a distal, concentrated nBCA plug during preoperative nBCA embolization of MSTs may increase tumor penetration and reduce IBL.

The correlation of cerebral arteriovenous malformation flow measured by quantitative MR angiography on MR-detected arteriovenous malformation microhemorrhage.

OBJECTIVE: The objective of this study was to assess the relationship of arteriovenous malformation (AVM) blood flow measured by quantitative MR angiography (QMRA) in nonruptured AVMs with MR-detected microhemorrhage. METHODS: All patients with unruptured AVMs who received baseline QMRA and gradient echo or susceptibility-weighted MRI were retrospectively reviewed (2004-2022). Imaging data, clinical history, and AVM angioarchitectural and flow features were collected and assessed. AVM flow was calculated from the difference of flow within primary arterial feeders from their contralateral counterparts. A review of the MR images determined the presence of microhemorrhages. Analysis of descriptive statistics, chi-square test, and binomial logistic regression were performed. RESULTS: Of 634 patients with cerebral AVMs at a single center, 89 patients met the inclusion criteria (54 with microhemorrhage and 35 without microhemorrhage). The calculated AVM flow was significantly higher in the group with a microhemorrhage (447.9 ± 193.1 ml/min vs 287.6 ± 235.7 ml/min, p = 0.009). In addition, the presence of venous anomaly, arterial ectasia, and diffuse nidus was significantly associated with microhemorrhage (p = 0.017, p = 0.041, and p = 0.041, respectively). Binary logistic regression found that higher flow predicted the presence of microhemorrhage (OR 1.002, 95% CI 1.000-1.004; p = 0.031). The highest AVM flow quartile significantly predicted the presence of venous anomaly (OR 3.840, 95% CI 1.037-14.213; p = 0.044), diffuse nidus (OR 6.800, 95% CI 1.766-25.181; p = 0.005), and arterial ectasia (OR 13.846, 95% CI 1.905-122.584; p = 0.018). CONCLUSIONS: This study represents the first to examine the association between flow measurements on QMRA with microhemorrhage in unruptured AVMs. Higher AVM flow, venous anomaly, arterial ectasia, and diffuse AVM nidus were related to a higher likelihood of AVM microhemorrhage. Higher AVM flow was present in AVMs with venous anomalies, a diffuse nidus, and arterial ectasia, indicating a possible interaction between these angioarchitectural findings, AVM flow, and microhemorrhage. These findings suggest a relationship between higher AVM flow and the risk of microhemorrhage.

Quantitative Blood Flow Reduction in Selective Embolization of Intranidal Fistula of Cerebral Arteriovenous Malformations: Case Series.

BACKGROUND AND OBJECTIVES: Arteriovenous malformations (AVMs) are often associated with high-flow intranidal fistulas (INFs). Although INF embolization has been suggested to provide higher reduction of total AVM flow compared with regular pedicle embolization, this effect has not previously been quantified. The aim of this study was to characterize the effect of AVM INF embolization on total AVM flow. METHODS: This study is an Institutional Review Board-approved, retrospective case series of patients from 2010 to 2022 with AVMs, both with and without INFs, who underwent quantitative magnetic resonance angiography and endovascular embolization. RESULTS: Twenty patients accounted for 35 separate embolization sessions: 13 patients with INFs underwent a total 21 embolizations and 12 patients without INFs had 14 embolizations. No significant differences were found between groups on age, sex, laterality, drainage pattern, and Spetzler-Martin grade. However, AVMs with INFs were larger than the control group (12.7 vs 8.37 cm 3 , P = .049). Baseline pre-embolization AVM flow significantly differed between AVM with INF vs control groups (522 vs 320 cc/min, P = .005). Similarly, postembolization AVM flow also differed between AVM with INF and control groups (392 vs 224 cc/min, P = .008), with a larger decrease in flow per vessel per embolization session within the AVM INF group compared with controls (101.5 vs 33.2 cc/min, P < .001). Repeated measure analysis of variance showed significant differences pre-embolization and postembolization AVM flow between those with INFs vs controls ( P < .001). CONCLUSION: This study represents the first to examine the effect of INF embolization on total AVM flow. AVMs with INFs showed higher baseline flow, and targeted embolization toward INFs significantly lowered AVM flow in comparison with controls without INFs. The results of this study emphasize the importance of recognizing the presence of INFs within AVMs and their embolization to reduce AVM flow as part of a multistep management paradigm.

Rupture-Risk Stratifying Patients with Cerebral Arteriovenous Malformations Using Quantitative Hemodynamic Flow Measurements.

Arteriovenous malformations (AVMs) are high-pressure, low-resistance arterial-venous shunts without intervening capillaries. Up to 60% of AVMs present with an intracranial hemorrhage; however, noninvasive neuroimaging has increasingly diagnosed incidental AVMs. AVM management depends on weighing the lifetime rupture risk against the risks of intervention. Although AVM rupture risk relies primarily on angioarchitectural features, measuring hemodynamic flow is gaining traction. Accurate understanding of AVM hemodynamic flow parameters will help endovascular neurosurgeons and interventional neuroradiologists stratify patients by rupture risk and select treatment plans. This review examines various neuroimaging modalities and their capabilities to quantify AVM flow, as well as the relationship between AVM flow and rupture risk. Quantitative hemodynamic studies on the relationship between AVM flow and rupture risk have not reached a clear consensus; however, the preponderance of data suggests that higher arterial inflow and lower venous outflow in the AVM nidus contribute to increased hemorrhagic risk. Future studies should consider using larger sample sizes and standardized definitions of hemodynamic parameters to reach a consensus. In the meantime, classic angioarchitectural features may be more strongly correlated with AVM rupture than the amount of blood flow.

Preoperative embolization of brain arteriovenous malformation and efficacy in intraoperative blood loss reduction: a quantitative study.

BACKGROUND: Embolization of brain arteriovenous malformations (bAVMs) is often used as adjuvant therapy to microsurgical resection to reduce the high-risk features of bAVMs such as large size and high flow. However, the effect of preoperative embolization on surgical performance and patient outcome has shown mixed results. Heterogeneity in treatment goals, selection criteria, and unpredictable changes in bAVM hemodynamics after partial embolization may account for these uncertain findings. In this study we use an objective quantitative technique to assess the impact of preoperative embolization on intraoperative blood loss (IBL). METHODS: Patients with bAVM treated with microsurgical resection only or in combination with preoperative embolization from 2012 to 2022 were retrospectively reviewed. Patients were included if quantitative magnetic resonance angiography was performed prior to any treatment. Correlation of baseline bAVM flow, volume, and IBL was evaluated between the two groups. Additionally, bAVM flow prior to and after embolization was compared. RESULTS: Forty-three patients were included, 31 of whom required preoperative embolization (20 had more than one session). Mean bAVM initial flow (362.3 mL/min vs 89.6 mL/min, p=0.001) and volume (9.6 mL vs 2.8 mL, p=0.001) were significantly higher in the preoperative embolization group; flow decreased significantly after embolization (408.0 mL/min vs 139.5 mL/min, p<0.001). IBL was comparable between the two groups (258.6 mL vs 141.3 mL, p=0.17). Linear regression continued to show a significant difference in initial bAVM flow (p=0.03) but no significant difference in IBL (p=0.53). CONCLUSION: Patients with larger bAVMs who underwent preoperative embolization had comparable IBL to those with smaller bAVMs undergoing only surgical treatment. Preoperative embolization of high-flow bAVMs facilitates surgical resection, reducing the risk of IBL.

Outcomes of patients undergoing single-level arthroplasty versus anterior lumbar interbody fusion.

BACKGROUND: Compared to vertebral body fusion, artificial discs are thought to lessen the risks of adjacent segment disease and the need for additional surgery by maintaining spinal mobility as they mimic the intervertebral disc structure. No studies have compared the rates of postoperative complications and the requirement for secondary surgery at adjacent segments among patients who have undergone anterior lumbar interbody fusions (ALIF) versus those undergoing lumbar arthroplasty. METHODS: An all-payer claims database identified 11,367 individuals who underwent single-level ALIF and lumbar arthroplasty for degenerative disc disease (DDD) between January 2010 and October 2020. Rates of complications following surgery, the need for additional lumbar surgeries, length of stay (LOS), and postoperative opioid utilization were assessed in matched cohorts based on logistic regression models. Kaplan-Meyer plots were created to model the probability of additional surgery. RESULTS: Following 1:1 exact matching, 846 records of patients who had undergone ALIF or lumbar arthroplasty were analyzed. All-cause readmission within 30-30 days following surgery was significantly higher in patients undergoing ALIF versus arthroplasty (2.6% vs. 0.71%, p = 0.02). LOS was significantly lower among the patients who had undergone ALIF (1.043 ± 0.21 vs. 2.17 ± 1.7, p < .001). CONCLUSIONS: ALIF and lumbar arthroplasty procedures are equally safe and effective in treating DDD. Our findings do not support that single-level fusions may biomechanically necessitate revisional surgeries.

Brain arteriovenous malformation flow after stereotactic radiosurgery: Role of quantitative MRA.

BACKGROUND: Stereotactic radiosurgery (SRS) is a current therapeutic option for treatment of arteriovenous malformations (AVMs) located in deep or eloquent brain regions. Obliteration usually occurs in a delayed fashion, with an expected latency of 3-5 years. Here, we assess how AVM flow correlates with volume before and after SRS treatment. METHODS: Patients with supratentorial AVM treated with SRS at our institution between 2012-2022 were retrospectively reviewed. Patients were included if Quantitative Magnetic Resonance Angiography (QMRA) study was performed at baseline and at least at the first follow-up. Correlation between AVM flow and volume before and after treatment was evaluated. AVM flow and volume were additionally assessed for obliteration using the non-parametric receiver operating characteristic (ROC) curve. RESULTS: Twelve patients with radiologic follow-up imaging were included. Eight patients presented AVM rupture, one of which occurred after radiosurgical treatment. Three patients underwent embolization prior SRS. Mean AVM initial volume was 3.8 cc (0.1-12.4 cc), mean initial flow 174 ml/min (11-604 ml/min), both variables showed progressive reduction at follow-up (range 3-57 months); and flow decreased with volume reduction (p < 0.001). Area under the ROC was 0.914 for both AVM flow and volume with obliteration (p = 0.019). CONCLUSIONS: AVM flow significantly decreased after SRS treatment, reflecting volume reduction. Baseline AVM flow and volume both predicted obliteration. QMRA provides additional non-invasive information to monitor patients after radiosurgical treatment.

Gender Disparities in Outpatient Management of Postlaminectomy Syndrome.

INTRODUCTION: Postlaminectomy syndrome (PLS), also known as failed back surgery syndrome, is the persistence of radicular pain in the face of surgical intervention. Despite its prevalence in 10 to 40% of spine surgery patients, outpatient pharmacologic and interventional management remains poorly characterized. METHODS: The 2007 to 2016 National Ambulatory Medical Care Survey (NAMCS) was utilized to include all outpatients diagnosed with PLS. For each visit, documented pain medications (opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], neuropathic agents, etc) as well as patient demographics and comorbidities (sex, age, race, insurance coverage, and medical history) were recorded. The association between medication class and rate of prescription relative to sex was assessed in the population-weighted cohort, using propensity score matching to control for potential confounders. RESULTS: A total of 70,343 PLS patients were identified, including 36,313 (51.6%) women. After accounting for baseline demographics and comorbidity differences between male and female patients, men were 2 to 3 times more likely to be prescribed opioids (OR: 2.38; 95%CI: 2.30-2.46) and procedural interventions for PLS compared to the female cohort, while women utilized neuropathic agents (OR: 0.53; 95%CI: 0.51-0.55) and NSAIDs (OR: 0.68; 95%CI: 0.65-0.70) more frequently. CONCLUSION: Pain management in outpatients presenting with PLS-related pain consisted of higher opioid utilization for men and higher neuropathic agents and NSAIDs utilization for the female patients. CLINICAL RELEVANCE: This article is the first to shed light on disparities in pain management among patients with post-laminectomy syndrome.

Tyrosine phosphatases regulate resistance to ALK inhibitors in ALK+ anaplastic large cell lymphoma.

Anaplastic large cell lymphomas (ALCLs) frequently carry oncogenic fusions involving the anaplastic lymphoma kinase (ALK) gene. Targeting ALK using tyrosine kinase inhibitors (TKIs) is a therapeutic option in cases relapsed after chemotherapy, but TKI resistance may develop. By applying genomic loss-of-function screens, we identified PTPN1 and PTPN2 phosphatases as consistent top hits driving resistance to ALK TKIs in ALK+ ALCL. Loss of either PTPN1 or PTPN2 induced resistance to ALK TKIs in vitro and in vivo. Mechanistically, we demonstrated that PTPN1 and PTPN2 are phosphatases that bind to and regulate ALK phosphorylation and activity. In turn, oncogenic ALK and STAT3 repress PTPN1 transcription. We found that PTPN1 is also a phosphatase for SHP2, a key mediator of oncogenic ALK signaling. Downstream signaling analysis showed that deletion of PTPN1 or PTPN2 induces resistance to crizotinib by hyperactivating SHP2, the MAPK, and JAK/STAT pathways. RNA sequencing of patient samples that developed resistance to ALK TKIs showed downregulation of PTPN1 and PTPN2 associated with upregulation of SHP2 expression. Combination of crizotinib with a SHP2 inhibitor synergistically inhibited the growth of wild-type or PTPN1/PTPN2 knock-out ALCL, where it reverted TKI resistance. Thus, we identified PTPN1 and PTPN2 as ALK phosphatases that control sensitivity to ALK TKIs in ALCL and demonstrated that a combined blockade of SHP2 potentiates the efficacy of ALK inhibition in TKI-sensitive and -resistant ALK+ ALCL.