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Supplemental Information. Additional Methods and Supplemental Figure Legends

Supplemental Tables 1 - 4. Supplemental Table 1: Patient characteristics for use in this study. Supplemental Table 2: Correlational bivariate analyses between ordinal variable clinicopathologic characteristics. Supplemental Table 3: Results of Cox Regression analysis using BALR-2, Translocation, and Prednisone Response as co-variates.

Radiation induced oral mucositis (RIOM) is a common and debilitating complication of radiation therapy for head and neck cancers. RIOM can lead to oral pain, dysphagia, and reduced oral intake, which can be severe enough to necessitate placement of a feeding tube or utilization of total parenteral nutrition. When severe, RIOM can cause premature termination of radiation therapy and can alter treatment plans leading to suboptimal treatment doses. While patient reporting of RIOM symptoms has been the gold standard of documenting RIOM progression, little has been described in the radiology literature concerning the typical imaging findings of RIOM. Herein, we review the pathophysiology and clinical presentation that underlies the development of RIOM with illustrative cases to highlight the relevant imaging findings related to RIOM for the practicing radiologist.

Occipital condylar avulsion fractures are considered potentially unstable, associated with craniocervical dissociation spectrum injuries, and thought to carry a relatively high mortality rate based on the current literature. The purpose of this study was to identify patient with acute, occipital condylar avulsion fractures and evaluate for the incidence of concomitant cervical osteoligamentous trauma and craniocervical dissociation spectrum injury on cervical spine CT and MRI. Patients who suffered an inferomedial occipital condylar avulsion fracture were identified retrospectively using Nuance mPower software. Cervical spine CT and MRI reports performed within 48 h for this patient cohort were then reviewed by two CAQ certified neuroradiologists. Confirmation of an occipital condylar avulsion fracture was recorded along with any concomitant craniocervical junction injury. Relevant clinical history, including management and outcomes, was recorded for each patient. Thirty-four patients were identified with an inferomedial fracture of the occipital condyle. Of the 85% of patients who underwent cervical MRI, all but one patient demonstrated a ‘negative’ MRI without major craniocervical junction ligamentous injury. These patients were treated conservatively with external bracing without persistent neurologic deficits upon 4-month follow-up. Inferomedial fractures of the occipital condyle are currently classified as potentially unstable fractures based on the Anderson classification system. Our data suggest that an isolated occipital condylar avulsion fracture without an additional C1–C2 fracture or widening of the atlanto-occipital joint space is likely a stable injury that can be treated conservatively with excellent clinical outcomes.

Mechanical thrombectomy (MT) is standard for acute ischemic stroke (AIS), with early studies suggesting that general anesthesia (GA) is associated with worse outcomes than monitored anesthesia care (MAC). Socioeconomic deprivation is also a risk factor for worse AIS outcomes. With improvements in MT and blood pressure (BP) management, it remains unclear if GA or socioeconomic deprivation are risk factors for worse outcomes after MT.We retrospectively analyzed 125 consecutive AIS patients presenting for MT at a comprehensive stroke center serving patients with high levels of socioeconomic deprivation. The primary objective was impact of GA versus MAC on functional independence at 90 days. Secondary outcomes included procedural BP, and impact of BP and socioeconomic deprivation (assessed by the area of deprivation index) on outcomes.A 90-day outcomes were similar in patients undergoing MT with GA or MAC. The area of deprivation index was similar in GA and MAC groups and in patients with good versus poor 90-day outcomes. There were similar numbers of patients with mean arterial pressure (MAP)60 mm Hg in the MAC and GA groups (8 vs. 11; P=0.21), but more patients with MAP70 mm Hg in the GA group (28 vs. 9; P0.001). Median (interquartile range) duration of MAP70 mm Hg was 10 (5 to 15) and 20 (10 to 36) minutes in the MAC and GA groups, respectively (P0.001); however, these MAPs were not associated with worse 90-day outcomes.Anesthesia and MAP did not affect MT outcomes. The cohort is unique based on an area of deprivation index in the higher deciles in the United States. While the area of deprivation index was not associated with worse outcomes, further study is warranted.

The falx cerebelli is a small crescent fold of dura mater that is attached to the internal occipital crest and projects forward into the posterior cerebellar notch between the cerebellar hemispheres. We report a rare case of a 61-year-old female who presented with a 1-month history of headache and gait instability. Imaging findings were suggestive of a meningioma arising from the falx cerebelli. Complete surgical resection was achieved with a standard posterior fossa midline approach. Duraplasty was performed using animal allograft dura (Duraguard) and additional layers of oxidized cellulose preparation (Surgicel), fibrin sealant, and nonsuturable collagen matrix (Duragen) were utilized to reduce the risk of a cerebrospinal fluid leak. Pathology confirmed a World Health Organization (WHO) grade-I meningioma. Postoperatively, patient with asymptomatic thrombosis of the left transverse/sigmoid sinuses and later with a pseudomeningocele managed with a lumbar drain. To our knowledge, this is the second documented case in the literature. We discuss intraoperative nuances and unique aspects in the postoperative care and management of these patients.

Purpose To evaluate the effectiveness of external-beam proton therapy (PT) on local control and survival in patients with skull-base chordoma. Materials and Methods We reviewed the medical records of patients with skull-base chordoma treated with definitive or adjuvant high-dose PT and updated their follow-up when feasible. We assessed overall survival, disease-specific survival, local control, and freedom from distant metastasis. Radiotherapy toxicities were scored using the Common Terminology Criteria for Adverse Events, version 4.0. Results A total 112 patients were analyzed, of whom 105 (94%) received PT and 7 (6%) received combined proton-photon therapy between 2007 and 2019. Eighty-seven patients (78%) underwent a subtotal resection, 22 (20%) a gross total resection, and 3 (3%) a biopsy alone. The median radiotherapy dose was 73.8 Gy radiobiologic equivalent (GyRBE; range, 69.6-74.4). Ninety patients (80%) had gross disease at radiotherapy and 7 (6%) were treated for locally recurrent disease following surgery. Median follow-up was 4.4 years (range, 0.4-12.6); for living patients, it was 4.6 years (range, 0.4-12.6), and for deceased patients, 4.1 years (range, 1.2-11.2). At 5 years after radiotherapy, the actuarial overall survival, disease-specific survival, local control, and freedom from distant metastasis rates were 78% (n = 87), 83% (n = 93), 74% (n = 83), and 99% (n = 111), respectively. The median time to local progression was 2.4 years (range, 0.8-7). Local control and disease-specific survival by resection status was 95% versus 70% (P = 0.28) and 100% versus 80% (P = 0.06) for gross total, versus subtotal, resection or biopsy alone, respectively. There were no serious acute toxicities (grade ≥ 3) related to radiotherapy. Conclusion High-dose PT alone or after surgical resection for skull-base chordoma reaffirms the favorable 5-year actuarial local control rate compared with conventional techniques with acceptable late-complication–free survival. Outcomes following gross total resection and adjuvant PT were excellent. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Post-transcriptional gene regulation, including that by RNA binding proteins (RBPs), has recently been described as an important mechanism in cancer. We had previously identified a set of RBPs that were highly dysregulated in B-cell acute lymphoblastic leukemia (B-ALL) with MLL translocations, which carry a poor prognosis. Here, we sought to functionally characterize these dysregulated RBP genes by performing a focused CRISPR dropout screen in B-ALL cell lines, finding dependencies on several genes including EIF3E, EPRS and USO1. Validating our findings, CRISPR/Cas9-mediated disruption of USO1 in MLL-translocated B-ALL cells reduced cell growth, promoted cell death, and altered the cell cycle. Transcriptomic analysis of USO1-deficient cells revealed alterations in pathways related to mTOR signaling, RNA metabolism, and targets of MYC. In addition, USO1-regulated genes from these experimental samples were significantly and concordantly correlated with USO1 expression in primary samples collected from B-ALL patients. Lastly, we found that loss of Uso1 inhibited colony formation of MLL-transformed in primary bone marrow cells from Cas9-EGFP mice. Together, our findings demonstrate an approach to performing focused sub-genomic CRISPR screens and highlight a putative RBP vulnerability in MLL-translocated B-ALL, thus identifying potential therapeutic targets in this disease.

Background & purpose Dose escalation for skull-based chordoma and chondrosarcoma can put critical adjacent structures at risk, specifically the anterior optic pathway. We report the incidence of vision loss following high-dose conformal proton-based radiotherapy. Materials and methods We reviewed patients with skull-base chordoma or chondrosarcoma treated with proton-based therapy between 2007 and 2018. We analyzed 148 patients and 283 individual eyes with functional vision at baseline who received a minimum 30GyRBE to 0.1 cm3 of the anterior optic pathway. Eyes were classified as “functionally blind” if visual acuity was 20/200 or worse. Kaplan-Meier and normal tissue complication probability modeling were used to establish the relationship between radiation dose and risk of functional vision loss. Results At last follow-up, 110 of 148 patients were alive with no evidence of disease progression. With a median follow-up of 4.1 years (range, 0.5–12.8), 5 eyes in 3 patients developed functional blindness, with 2 patients developing bilateral blindness. Median time to blindness was 15.2 months. The 5-year incidence of vision loss was 2.1% (95% CI: 0.9–4.9%). On univariate analysis, development of blindness was associated with presence of multiple medical comorbidities (p = 0.0040). While there were no events with a maximum dose Conclusions Despite the high radiotherapy dose delivered to patients with skull-base chordoma and chondrosarcoma, the rate of vision loss is low and no events occurred in those who received a maximum dose under 60GyRBE.

The NCCN Guidelines for Acute Myeloid Leukemia (AML) provide recommendations for the diagnosis and treatment of adults with AML based on clinical trials that have led to significant improvements in treatment, or have yielded new information regarding factors with prognostic importance, and are intended to aid physicians with clinical decision-making. These NCCN Guidelines Insights focus on recent select updates to the NCCN Guidelines, including familial genetic alterations in AML, postinduction or postremission treatment strategies in low-risk acute promyelocytic leukemia or favorable-risk AML, principles surrounding the use of venetoclax-based therapies, and considerations for patients who prefer not to receive blood transfusions during treatment.

Despite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes. Here, we find that the RNA-binding protein IGF2BP3, which is overexpressed in MLL-translocated leukemia, strongly amplifies MLL-Af4-mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4-driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. At the molecular level, IGF2BP3 regulates a complex posttranscriptional operon governing leukemia cell survival and proliferation. IGF2BP3-targeted mRNA transcripts include important MLL-Af4-induced genes, such as those in the Hoxa locus, and the Ras signaling pathway. Targeting of transcripts by IGF2BP3 regulates both steady-state mRNA levels and, unexpectedly, pre-mRNA splicing. Together, our findings show that IGF2BP3 represents an attractive therapeutic target in this disease, providing important insights into mechanisms of posttranscriptional regulation in leukemia.

Aging-related chronic inflammation is a risk factor for many human disorders through incompletely understood mechanisms. Aged mice deficient in microRNA (miRNA/miR)-146a succumb to life-shortening chronic inflammation. In this study, we report that miR-155 in T cells contributes to shortened lifespan of miR-146a−/− mice. Using single-cell RNA sequencing and flow cytometry, we found that miR-155 promotes the activation of effector T cell populations, including T follicular helper cells, and increases germinal center B cells and autoantibodies in mice aged over 15 months. Mechanistically, aerobic glycolysis genes are elevated in T cells during aging, and upon deletion of miR-146a, in a T cell miR-155-dependent manner. Finally, skewing T cell metabolism toward aerobic glycolysis by deleting mitochondrial pyruvate carrier recapitulates age-dependent T cell phenotypes observed in miR-146a−/− mice, revealing the sufficiency of metabolic reprogramming to influence immune cell functions during aging. Altogether, these data indicate that T cell–specific miRNAs play pivotal roles in regulating lifespan through their influences on inflammaging.

Summary Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA CDK6-AS1 able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. CDK6-AS1 silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued. This latter phenomenon derived from RUNX1 transcriptional control, responsible for the stemness of hematopoietic precursors and for the block of differentiation in AML. By CDK6-AS1 silencing in vitro, AML mitochondrial mass decreased with augmented pharmacological sensitivity to mitochondria-targeting drugs. In vivo, the combination of tigecycline and cytarabine reduced leukemia progression in the AML-PDX model with high CDK6-AS1 levels, supporting the concept of a mitochondrial vulnerability. Together, these findings uncover CDK6-AS1 as crucial in myeloid differentiation and mitochondrial mass regulation., Graphical abstract, Highlights • CDK6-AS1 acts in concert with CDK6 • High CDK6-AS1 levels trigger RUNX1 early differentiation arrest in myeloid cells • CDK6-AS1 controls mitochondrial mass of AML blasts • CDK6-AS1 levels impact on mitochondrial-targeted agents sensitivity, Molecular biology; Cell biology; Cancer

Background and Purpose: Identify patients with a dorsal epidural hematoma at C1-C2 and examine the major craniocervical junction ligaments for injury on follow-up magnetic resonance imaging. Materials and Methods: Adult and pediatric trauma patients who suffered a dorsal epidural hematoma at C1-C2 were identified using Nuance mPower software (Nuance Communications, United States). The cervical computed tomography and magnetic resonance imaging exams for these patients were reviewed for craniocervical junction osteoligamentous injuries. An age-matched control group was obtained. Results: Eight trauma patients were identified with a dorsal epidural fluid collection at C1-C2. All patients with a dorsal epidural hematoma, who underwent follow-up cervical magnetic resonance imaging demonstrated a stripping injury of the posterior atlanto-occipital membrane from the C1 posterior arch with increased short tau inversion recovery signal in the posterior atlanto-occipital membrane complex. Disruption of additional major craniocervcial ligaments on magnetic resonance imaging was relatively common with the most frequently associated ligamentous injuries involving the tectorial membrane (five patients) followed by the alar ligaments and anterior altanto-occiptial membrane (four patients each). Conclusions: A C1-C2 dorsal epidural hematoma is a rare injury that may be identified on cervical spine computed tomography but may be easily overlooked by the radiologist. We propose that a C1-C2 dorsal epidural hematoma is a direct result of a significant hyperflexion-hyperextension force with subsequent stripping of the posterior atlanto-occipital membrane from the posterior C1 arch. Trauma patients with a C1-C2 dorsal epidural hematoma on cervical spine computed tomography should undergo a cervical magnetic resonance imaging examination to evaluate the integrity of the posterior atlanto-occipital membrane complex and remaining craniocervical junction ligaments for injury.

Intravesical administration of bacille Calmette-Guerin (BCG) is an important component of the gold standard in treating non-muscle invasive bladder cancer (NMIBC). However, complications of this treatment include infections caused by the dissemination of Mycobacterium bovis. We present a case of a 62-year-old man who had been treated with intravesical BCG for bladder cancer and developed an M. bovis infection of his vertebral column. About four months after completing the BCG treatment, he developed an acute onset of severe upper thoracic radicular back pain, with radiation anteriorly to his sternum. Examination revealed the presence of early myelopathy. After other causes were ruled out, he was diagnosed with the infection four months later. He was investigated for the pain, with resulting imaging identifying an erosive ventral epidural mass at the T4-T5 levels causing cord compression. The patient underwent a transthoracic procedure to evacuate the paraspinal mass lesion and obtain a diagnostic biopsy, followed by a posterolateral decompression of the lesion and posterior instrumented stabilization. Pathology resulted in the identification of a granuloma with a single acid-fast bacillus (AFB) from the paraspinal abscess, thus being diagnostic of a mycobacterial granuloma with paraspinal involvement. We subsequently performed an extensive review of current literature, looking at articles on spinal osteomyelitis following intravesical BCG treatment of bladder cancer. We identified 26 documented cases in English literature. We present our case report with a good outcome at 24 months, resolving with appropriate chemotherapy. Additionally, we completed a systematic review of the literature and discuss this infrequent iatrogenic pathology. Our report reveals the good response to targeted therapy in the case of osteomyelitis at other skeletal sites and that practitioners caring for these patients maintain a high degree of suspicion in the workup of these patients. Early identification and treatment can appropriately treat osteomyelitis with good long-term outcomes.

Chordomas of the skull-base are typically slow-growing, notochord-derived tumors that most commonly originate along the clivus. Skull base chordoma is treated with surgery and radiotherapy. Local recurrence approaches 50% at 10 years. Radiologists play a critical role in diagnosis, treatment planning, and follow-up. Surgeons and radiation oncologists rely on radiologists for pre-operative delineation of tumor and adjacent anatomy, identification of post-treatment changes and disease recurrence, and radiation treatment effects. This review provides an overview of clinical characteristics, surgical anatomy, indications for radiotherapy, identification of treatment complications, and patterns of disease recurrence for radiologists to provide value in the management of these lesions.

BACKGROUIND Chiari malformations include a spectrum of congenital hindbrain herniation syndromes. In patients with the most common subtype, Chiari malformation Type I, 50% to 75% develop a syrinx. The pathogenesis of syringomyelia is not well understood, with multiple theories outlined in the literature. Although the presence of a syrinx in a patient with Chiari malformation is generally accepted as an indication for surgical intervention, there are documented cases of spontaneous resolution that support a more conservative approach to management. OBSERVATIONS The authors reported a case of spontaneous resolution of a cervical syrinx in an adult with an unchanged Chiari malformation. LESSONS Given the possibility of spontaneous resolution over time, the authors believe a more conservative approach of observation with periodic surveillance, magnetic resonance imaging, and neurological examination should be considered in the management of a patient with a Chiari malformation and associated syringomyelia.

Dental infections are a common presentation in the emergency department (ED). To help guide clinical management for these infections, the radiologist must be familiar with the anatomy of the oral cavity and neighboring structures, the range of appearance of dental infections, and the routes along which they may spread. Computed tomography (CT) is often performed when severe dental infections are suspected. This pictorial essay reviews the anatomy pertinent to the imaging evaluation of dental infections and depicts a spectrum of pathology that may be encountered, ranging from simple dentoalveolar infections to complex multispatial infections.

The role of personality traits in modulating the incidence and progression of medical disease conditions are well documented, however, there is a paucity of information for its effects on dental health conditions and specifically on the prognosis of restorative dental materials. This study aims to evaluate the clinical performance of Micro-hybrid and Nano-ceramic composite restorations among patients with different personality traits. A total of 323 patients, indicated to receive operative treatment at a University Dental College Hospital, were invited to participate in this study. Consenting patients were requested to complete the Big Five Inventory (BFI-44 Item) personality questionnaire and were evaluated by a psychiatrist for categorizing the participants based on their personality traits. Out of the recruited patients, 124 patients falling in to the dominant trait of Agreeableness (n = 62) and Neuroticism (n = 62) were included in the study for further investigation. Next, patients from the Agreeableness (Group A) and the Neuroticism personality trait group (Group N) were randomly divided into two subgroups each—sub group Am (n = 44) and Nm (n = 48) for Micro-hybrid composite restorations and Sub group An (n = 42) and Nn (n = 47) for Nano-ceramic composite restorations. Two trained and calibrated dentists prepared the cavities according to previously published methodology. The restorations were evaluated at baseline (immediately after restoration), 6-months, 12-months and 24-months intervals by two blinded independent dental professionals for anatomical form, secondary caries, color match, retention, marginal adaptation, surface texture, marginal discoloration and post-operative sensitivity. There is no statistically significant difference noted in various parameters of restoration performance between Micro-hybrid composite and Nano-ceramic composite compared among ‘agreeableness’ personality group and among ‘neuroticism’ personality group after controlling the personality trait factor. Higher ‘Neuroticism’ individuals had higher restoration deterioration in color matching and surface texture when compared to higher ‘Agreeableness’ trait individuals. Regression analysis showed no effect of gender or cavity size on the outcome of results. Assessment of personality traits may serve as a useful tool during treatment planning which would aid clinicians in choosing suitable restorative dental material and prosthesis design according to individual patient’s physiological and functional needs, thereby overall improving the quality of treatment provided.

Background In the absence of frank craniocervical dissociation, there is a lack of consensus regarding what patterns of craniocervical junction ligamentous injuries require occipital-cervical fusion. This study was undertaken to examine the integrity of the craniocervical junction ligaments and analyze clinical outcomes in patients who underwent occipital-cervical fusion for craniocervical junction injury. Methods Adult patients requiring occipital-cervical fusion were identified retrospectively utilizing keyword searches in cervical computed tomography and magnetic resonance imaging reports between 2012 and 2020 using Nuance mPower software (Nuance, Burlington, MA). The cervical magnetic resonance imaging examinations for these patients were reviewed for craniocervical ligamentous injury by two neuroradiologists. Descriptions of craniocervical junction injuries, demographic information, clinical history, surgical management, and global outcomes were recorded. Results Nine adult patients were identified with an acute, post-traumatic craniocervical junction injury requiring occipital-cervical fusion. All nine patients demonstrated a ligamentous tear in at least one of the four major craniocervical junction ligaments - the occipital condylar-C1 capsular ligaments, alar ligaments, tectorial membrane, and posterior atlantooccipital membrane. The tectorial membrane was the most commonly torn ligament followed by the alar ligament(s), posterior atlantooccipital membrane, and capsular ligament(s). There was wide variability in the number of major craniocervical junction ligaments torn, ranging from one ligament to all four ligaments. Four patients suffered persistent neurologic deficits following surgery. Conclusion Craniocervical injury is best evaluated by cervical magnetic resonance imaging. In the absence of overt craniocervical dissociation, we propose that an injury of the tectorial membrane in the adult population may indicate patients with significant craniocervical instability, possibly necessitating occipital-cervical fusion.

Hypertrophic olivary degeneration is a rare condition caused by a lesion in the Guillain-Mollaret triangle which leads to trans-synaptic degeneration resulting in the degenerative hypertrophy of the inferior olivary nucleus. This condition presents clinically with palatal tremor but can also produce ocular myoclonus or cerebellar signs. While any lesion that occurs within the Guillian-Mollaret triangle and results in the deafferentation of the inferior olive can lead to hypertrophic olivary degeneration, the most common etiologies include ischemic and hemorrhagic stroke, vascular malformation, neoplasm, and iatrogenic injury related to surgery. We report a series of 7 patients who presented with this condition bilaterally on MRI imaging, including 1 case which represents the first report of toxoplasmosis leading to the development of bilateral hypertrophic olivary degeneration and only the third reported case, unilateral or bilateral, related to an infectious etiology.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a rare occurrence. We present a case of spontaneous CSF rhinorrhea in a 57-year-old patient secondary to a sphenoid osseous defect involving the foramen rotundum and maxillary nerve with an associated arachnoid cyst and meningocele compressing the maxillary nerve. The location of the defect made correction amenable to an open skull-based approach. To the best of our knowledge, this is the first reported case of a spontaneous meningocele herniating into the sphenoid osseous defect through the medial aspect of the foramen rotundum. Early detection of these defects, open or endoscopic approaches and definitive treatment by closing the defect can result in excellent outcomes.

Traumatic tectorial membrane injuries have different radiologic presentations in adult versus pediatric patients. The purpose of this study was to identify and classify the different types of tectorial membrane injuries that occur in the adult and pediatric populations. Patients who suffered tectorial membrane injury were identified retrospectively using the keywords ‘tectorial membrane,” “craniocervical ligament tear/injury,” and “atlanto-occipital dissociation” included in radiology reports between 2012 and 2018 using Nuance mPower software. All relevant imaging studies were reviewed by two certificates of additional qualification-certified neuroradiologists. Detailed descriptions of injuries were recorded along with any relevant additional findings, including clinical history. Ten adults and six pediatric patients were identified with acute traumatic injuries of the tectorial membrane. Ninety percent of the adult patients sustained complete disruptions inferior to the clivus, or subclival, with 22% of tears at the level of the basion and 78% at the level of the odontoid tip. In contrast, 83% of pediatric patients suffered a stripping injury of the tectorial membrane located posterior to the clivus, or retroclival. Stretch injuries of the tectorial membrane were identified in 10% of adults and 17% of pediatric patients. The juvenile-type injury, which causes retroclival epidural hematoma, was determined to preferentially occur in patients less than or equal to 14 years of age with a high level of statistical significance (p value = 0.0014). A classification system for tectorial membrane injuries is proposed based on this data: type 1—retroclival stripping injury (more common in pediatric patients); type 2a—subclival disruption at the basion and type 2b—subclival disruption at the odontoid (both more common in adult patients); and type 3—thinning of the tectorial membrane.

We sought to evaluate the effectiveness of definitive or adjuvant external-beam proton therapy on local control and survival in patients with skull-base chondrosarcoma. We reviewed the medical records of 43 patients with a median age of 49 years (range, 23–80 years) treated with double-scattered 3D conformal proton therapy for skull-base chondrosarcomas between January 2007 and February 2016. Proton therapy-related toxicities were scored using CTCAE v4.0. The median radiotherapy dose was 73.8 Gy(RBE) (range, 64.5–74.4 Gy[RBE]). Thirty-six (84%) and 7 (16%) patients underwent surgical resection or biopsy alone. Tumor grade distribution included: grade 1, 19 (44%) patients; grade 2, 22 (51%); and grade 3, 2 (5%). Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following surgery. The median follow-up was 3.7 years (range, 0.7–10.1 years). There were no acute grade 3 toxicities related to RT. At 4 years following RT, actuarial rates of overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were 95%, 100%, 89%, and 95%. High-dose, double-scattered 3D conformal proton therapy alone or following surgical resection for skull-base chondrosarcoma is an effective treatment with a high rate of local control with no acute grade 3 radiation-related toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Background: Liposarcoma (LPS) is an understudied form of soft tissue sarcoma (STS). The well-differentiated (WD) and de-differentiated (DD) subtypes of LPS are associated with indolent and aggressive disease courses, respectively, but this histologic stratification fails to fully capture disease heterogeneity. Molecular approaches may help refine prognostication and inform treatment intensification. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3 or IMP3), is an RNA-binding protein that regulates gene expression by controlling mRNA stability and has been implicated in tumorigenesis and poor prognosis in many cancers. We hypothesized IGF2BP3 would refine the prognostication of LPS beyond its WD/DD histologic status. Methods: We examined the association between IGF2BP3 gene or protein expression and clinical data in four datasets: (1) patients with STS subtypes (n=206) in the cancer genome atlas (TCGA) database, (2) an in-house gene microarray of lipomatous tumors (n=71), LPS cell lines (n=3) and patient-derived xenografts (PDX, n=3), (3) an in-house tissue microarray (TMA) of lipomatous tumors (n=115), LPS cell lines (n=3) and PDXs (n=3) and (4) an in-house TMA of WD/DD LPS (n=71). IGF2BP3 protein expression in TMAs was quantified by immunohistochemistry (IHC). IGF2BP3 gene and protein expression values from identical samples were compared by Pearson correlation (n=43). The Kaplan-Meier method and log-rank test were used to compare survival outcomes. Results: In the TCGA cohort, which does not include WD LPS, IGF2BP3 expression was a poor prognostic factor solely in DD LPS (n=50, median overall survival (mOS): 1.6 vs 5.0 years, p=0.009). Among gene microarray samples, IGF2BP3 expression was highest in DD LPS (n=18) compared to WD LPS (n=29) and lipoma (n=7) by paired t-tests (p=0.03 and 0.002, respectively) and IGF2BP3 expression was associated with worse survival in WD/DD LPS (mOS 7.7 vs 21.5 years, p=0.02). In both TMAs, IGF2BP3 expression (>25% cell positivity/core) portended worse survival in WD/DD LPS (mOS (3): 3.7 vs 13.8 years, p Conclusion: IGF2BP3 is highly expressed in a subset of LPS. Across independent datasets, IGF2BP3 is also a biomarker of disease progression and worse survival, and may stratify patients more effectively than histologic differentiation. Mechanistic studies of IGF2BP3 in LPS tumorigenesis and progression using aforementioned LPS cell lines and PDX models are ongoing. Citation Format: Kyle D. Klingbeil, Jack Pengfei Tang, Sarah M. Dry, Fritz C. Eilber, Dinesh S. Rao, Brian E. Kadera, Anusha Kalbasi. IGF2BP3 (IMP3) expression is associated with worse survival in well-differentiated/dedifferentiated (WD/DD) liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3490.

The supradental space is a small, predominantly fat-filled recess superior to the atlanto-axial joint and inferior to the basion of the clivus that contains a small venous plexus. The posterior boundary of the supradental space is formed by the tectorial membrane, a stabilizing ligament of the craniocervical junction. The purpose of our study was to examine the imaging appearance of the supradental space in patients with tectorial membrane injury. Adult patients with tectorial membrane injury were identified utilizing keyword searches of radiology reports using Nuance mPower software. Age-matched positive and negative control groups were obtained. Two CAQ-certified neuroradiologists evaluated the cervical CT exams of these patients for supradental fat pad effacement from hematoma formation. The integrity of the osteoligamentous structures of the craniocervical junction was recorded on CT and MRI exams along with demographic information, clinical history, surgical management, and global outcome. Statistical analysis was performed. Sixteen adults were diagnosed with tectorial membrane injury on cervical MRI. All patients with a visible supradental space demonstrated fat pad effacement and Hounsfield units consistent with hematoma formation. The positive and negative control groups demonstrated supradental fat pad effacement in 2/16 and 1/16 patients, respectively. A p-value of

Angiotensin-converting enzyme inhibitors (ACE-i) are commonly used medications to treat hypertension and congestive heart failure. Angioedema is a well-established side effect of ACE-i and most commonly manifests as swelling of the mucosal and extra-mucosal soft tissues in the head and neck. CT with contrast is generally used to evaluate for airway compromise and to exclude other etiologies of edema. Herein we present five cases that illustrate the radiological findings specific to ACE-i-induced angioedema on enhanced CT scans.

Background The posterior atlantooccipital membrane complex consists of the posterior atlantooccipital membrane and posterior atlantoaxial membrane. Posttraumatic, posterior atlantooccipital membrane complex injuries may have varied appearances on cervical magnetic resonance imaging. The purpose of this study was to identify the different types of posterior atlantooccipital membrane complex injuries that occur in trauma patients. Methods Patients who suffered a posterior atlantooccipital membrane complex injury were identified retrospectively using key word searches of cervical magnetic resonance imaging reports between 2013 and 2020 using Nuance mPower software. All relevant imaging studies were reviewed by 2 neuroradiologists. A description of the location and type of posterior atlantooccipital membrane complex injury was recorded, along with additional osteoligamentous trauma of the craniocervical junction and relevant clinical history. Results Forty-one patients were identified with acute posterior atlantooccipital membrane complex injury. Four distinct patterns of posterior atlantooccipital membrane complex injury were observed. Conclusions A grading system for posterior atlantooccipital membrane complex injuries is proposed on the basis of these data: grade 1—edema confined to the posterior atlantooccipital and atlantoaxial membrane; grade 2—edema confined to the posterior atlantooccipital and atlantoaxial membrane and ligamentum nuchae; grade 3—stripping injury of the posterior atlantooccipital membrane with C1-C2 dorsal epidural hematoma; and grade 4—frank disruption of the posterior atlantooccipital membrane at C1 with edema in the remaining posterior atlantooccipital membrane complex.

We report a case of a patient with a carotid body tumor with perineural tumor spread along the right superior laryngeal nerve. Perineural spread is most commonly associated with squamous cell, adenoid cystic, and mucoepidermoid carcinoma. To the best of our knowledge, this has not been reported previously with carotid body tumor.

Despite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes and a high risk of relapse. Here, we found that MLL-AF4, the most common MLL fusion protein in patients, transcriptionally induces IGF2BP3 and that IGF2BP3 strongly amplifies MLL-Af4 mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4 driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. eCLIP and transcriptome analysis of MLL-Af4 transformed stem and progenitor cells and MLL-Af4 bulk leukemia cells reveals a complex IGF2BP3-regulated post-transcriptional operon governing leukemia cell survival and proliferation. Regulated mRNA targets include important leukemogenic genes such as those in the Hoxa locus and numerous genes within the Ras signaling pathway. Together, our findings show that IGF2BP3 is an essential positive regulator of MLL-AF4 mediated leukemogenesis and represents an attractive therapeutic target in this disease.

The craniocervical junction (CCJ) is a complex and unique osteoligamentous structure that balances maximum stability and protection of vital neurovascular anatomy with ample mobility and range of motion. With the increasing utilization and improved resolution of cervical magnetic resonance imaging, craniocervical injury is being more accurately defined as a spectrum of injury that ranges in severity from overt craniocervical disassociation to isolated injuries of one more of the craniocervical ligaments, which may also lead to craniocervical instability. Thus, it is vital for the radiologist and neurosurgeon to have a thorough understanding of the imaging anatomy and function of the CCJ.

Craniotomy, or a surgical opening into the skull, has been observed as early as Paleolithic and Neolithic periods. Early craniotomies carried great morbidity and mortality and standardized during the 20th century, improving surgical outcomes. The simultaneous evolution of medical imaging and stereotactic navigation systems has allowed imaging to correlate findings with surgical approaches, further optimizing patient safety. We review the history of craniotomy and provide an imaging review of the most common craniotomy approaches.

Background and purpose The classic sign of a lesion in the medial longitudinal fasciculus is internuclear opthalmoplegia. However, clinical presentation may vary depending on the type of pathology and the lesion location. The purpose of this study was to identify and classify the different lesions of the medial longitudinal fasciculus on MRI and review their clinical presentations. We also offer an overview of the pertinent imaging anatomy of the medial longitudinal fasciculus. Materials and methods Patients with an abnormality affecting the medial longitudinal fasciculus were identified retrospectively using the keyword ‘medial longitudinal fasciculus’ included in radiology reports between 2010 and 2018 using the Nuance mPower software (Nuance Communications, Burlington, MA). The brain MRI examinations of these patients were reviewed by two neuroradiolgists. Detailed description of lesion location within the medial longitudinal fasciculus, pathology type, additional lesions, and clinical presentations were recorded along with pertinent demographic information. Results Five men and four women were identified with lesions in the medial longitudinal fasciculus on brain MRI. Five patients demonstrated demyelination in the medial longitudinal fasiculus and four patients demonstrated findings of an acute cerebrovascular accident. Two-thirds of medial longitudinal fasiculus lesions were located in the upper, mid, or lower pons with the remaining located in the midbrain. Of the patients presenting with a cerebrovascular accident, there was little to no additional evidence of acute stroke elsewhere in the brain. All patients were clinically symptomatic with 89% of patients demonstrating extraocular muscle dysfunction at presentation and 78% of patients experiencing dizziness. Additional symptoms included headache, weakness, and gait instability. Conclusions Lesions involving the medial longitudinal fasiculus may not always present with the classic sign of internuclear opthalmoplegia. Variations in lesion location may result in diplopia rather than internuclear opthalmoplegia, and additional brain lesions may produce clinical symptoms that confound extraocular muscle dysfunction. Lesions affecting the often-overlooked vestibular and otolithic reflexes, which run in the medial longitudinal fasiculus, may result in dizziness/weakness and mask the classic internuclear opthalmoplegia symptoms. The radiologist should carefully inspect the medial longitudinal fasiculus in all patients regardless of the supportive clinical history of extraocular muscle dysfunction since symptoms may be more general than classically described.

Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and adult patients, including vision loss and pituitary/hypothalamic dysfunction. Most craniopharyngioma series focus on treatment of the pediatric population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response.We analyzed 14 adult patients (≥ 22 years old). All patients had gross disease at the time of radiotherapy. Five were treated for de novo disease and 9 for recurrent disease. Patients received double-scattered conformal proton therapy to a mean dose of 54 GyRBE in 1.8 GyRBE/fraction (range 52.2-54 GyRBE). Weekly magnetic resonance imaging (MRI) helped to evaluate tumor changes during radiotherapy.With median clinical and radiographic follow-up of 29 and 26 months, respectively, the 3-year local control and overall survival rates were both 100%. There were no grade 3 or greater acute or late radiotherapy-related side effects. There was no radiotherapy-related vision loss or optic neuropathy. No patients required intervention or treatment replanning due to tumor changes during radiotherapy. Two patients experienced transient cyst expansion at their first post-radiotherapy MRI. Both patients were followed closely clinically and radiographically and had subsequent dramatic tumor/cyst regression, requiring no interventions.Our data support the safety and efficacy of proton therapy in the treatment of adult craniopharyngioma as part of primary or salvage treatment. We recommend early consideration of radiotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03224767.

We evaluated treatment outcomes following definitive or adjuvant high-dose, image-guided proton therapy in 91 patients with skull-base chordoma enrolled on a prospective outcomes tracking protocol and treated between February 2007 and February 2018. The median age was 53 years (range, 22–78 years). Patients received passively scattered 3-dimensional conformal proton therapy to a median dose of 73.8 GyRBE (range, 69.6–75.6 GyRBE). Two patients received a component of intensity-modulated radiotherapy. Seventy percent (n=64) were men and 30% (n=27) were woman. Eighty-two percent (n=75) of patients had macroscopic disease at the time of radiotherapy; 18% (n=16) had undergone a macroscopic gross total resection. Overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were calculated. Proton therapy-related toxicities were scored using CTCAE v4.0. With a median follow-up of 3.7 years (range, 0.2–10 years), 26 patients experienced disease recurrence, including 26 local, 0 regional, and 1 distant recurrence. The median time to local progression was 2.2 years (range, 0.4–7.0 years). At the time of last follow-up, 66 patients were alive (56 with no evidence of disease progression) and 25 were deceased (18 with disease progression). There were no acute grade 3 toxicities related to the radiation therapy. The 4-year actuarial rates of overall survival, cause-specific survival, local control, and radiation therapy-related grade 3 toxicity-free survival were 83%, 87%, 76% and 83%, respectively. Definitive or adjuvant high-dose passively scattered 3-dimensional conformal proton therapy for skull-base chordoma provides acceptable local control, comparing favorably to historic photon data, with no acute grade ≥3 radiation-related toxicity and an acceptable rate of grade ≥3 late toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Purpose To review the impact of a weekly multidisciplinary neuroradiology imaging review on the management of patients undergoing radiotherapy. Methods A prospective study of the management of 118 patients (30=head and neck, 40=skull base, central nervous system=48) was conducted over a 12-month period from January 2018 through January 2019. After review of each patient's history and relevant imaging, a radiation oncologist completed a form detailing the changes that were made in diagnosis and management. Imaging source (external and internal examinations), availability of outside reports, report timeliness, the value of reports, changes in interpretation, changes in clinical management, and changes in prognosis were documented. Changes in interpretation and management were designated as major or minor depending on the significance of the change. The managing radiation oncologist indicated whether the imaging review conference substituted for a peer-to-peer consultation with a neuroradiologist. Results Nearly half (47%) of all patients had a change in interpretation. Of those, 32% of patients had a major change in interpretation, while 14% had a minor change in interpretation. The existence of the multidisciplinary imaging review conference prevented a peer-to-peer consultation (interruption) by the radiation oncologists to the neuroradiologists in 90% of the cases presented. Further analysis was performed. Conclusion The involvement of neuroradiologists in a joint radiation oncology imaging review conference resulted in changes in diagnostic imaging interpretation that led to significant changes in management, expected prognosis, and workflow.