Vibhute, Prasanna

Abstract BACKGROUND MYCN-amplified spinal ependymoma is a recently classified, rare, and aggressive subtype of spinal cord tumor, first defined by the 2021 WHO CNS5 classification. It predominantly affects adults in their 30s, with a slight female predominance; fewer than 50 cases have been reported worldwide. PURPOSE To characterize the molecular, imaging, and clinical features of MYCN-amplified spinal ependymomas and highlight their distinctiveness to aid in early diagnosis and therapeutic planning. METHODS We retrospectively reviewed institutional cases of MYCN-amplified spinal ependymomas and performed a literature-based analysis. Data on imaging, histopathology, molecular profiles, and clinical outcomes were examined to identify distinguishing diagnostic and prognostic features. RESULTS These tumors are typically present as intradural extramedullary masses, often in the thoracic spine, with intense contrast enhancement and prominent peritumoral edema. A lack of a clear cleavage plane with the spinal cord, early leptomeningeal, and intracranial dissemination are hallmark features. Rare reports of systemic metastases (e.g., to the humerus and paraspinal muscle) exist. Histologically, they are high-grade (WHO grade III) anaplastic ependymomas with a distinct DNA methylation profile. MYCN amplification—commonly seen in medulloblastomas and glioblastomas—drives tumor aggressiveness. Clinically, these tumors are refractory to standard treatments, with high rates of recurrence or progression within 1–2 years post-treatment. The median overall survival is approximately seven years, significantly poorer than conventional spinal ependymomas. CONCLUSION MYCN-amplified spinal ependymomas represent a rare but highly aggressive tumor subtype with unique imaging, histological, and molecular features. Early recognition is critical given rapid progression and poor prognosis. Investigational therapies targeting MYCN—such as HDAC, PARP, Aurora A-kinase, and BET inhibitors—hold promise for improved outcomes.

Despite their similar nomenclature, Neurofibromatosis type 1 (NF1) and “Neurofibromatosis type 2” are discrete and clinically distinguishable entities. The name of “neurofibromatosis type 2” has been changed to NF2-related schwannomatosis, to reflect the fact that neurofibromas do not occur in this syndrome and therefore the name “Neurofibromatosis” is factually incorrect. Furthermore, multiple schwannomas, a hallmark feature of NF2, can also occur in patients with mutations in genes including SMARCB1 and LZTR1, all exhibiting overlapping clinical features. Current understanding suggests that schwannomatosis (SWN) encompasses a range of clinical presentations consisting of clearly defined, separate subtypes which share a common phenotype of schwannomas. Recognizing these newly emerging subtypes, the International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC) proposed a revised nomenclature for NF2 and related disorders in 2022. This review article focuses on this critical update in diagnostic terminology, highlighting the key gene-related SWN subtypes relevant to neuroradiologists. By emphasizing molecular testing alongside clinical features, the revised system facilitates a more precise diagnosis, potentially paving the way for personalized treatment strategies. Additionally, the flexible structure accommodates future discoveries of genes associated with SWN.

Takayasu arteritis is a chronic inflammatory vasculitis with granulomatous panarteritis particularly impacting large vessels including the aorta and its branches, especially the subclavian arteries, with clinical manifestation dependent on the involved artery. Sequelae of the active disease vary, including stenosis, occlusions, or aneurysmal dilatations of the large vessels. The prevalence of Takayasu arteritis is higher in the Asian population and in Japan, but quite low in the United States, varying from 0.9–8.4 per million people. Ocular manifestations are rare and lead to a delay in diagnosis and appropriate treatment. Ocular manifestations include Takayasu retinopathy, anterior ischemic optic neuropathy (AION), retinal artery occlusion (RAO) and retinal vein occlusion (RVO). We present two cases in which central retinal artery occlusion (CRAO) was associated with Takayasu arteritis. CRAO is an ophthalmic emergency with an incidence of 1.9 per 100,000 person years in the United States; only 5% of cases are arteritic, which can be observed with inflammatory vasculitides secondary to the formation of immune deposits.

Abstract Introduction: Radiation therapy (RT) is the standard of care for central nervous system (CNS) cancers. Despite the success of RT in reducing tumor mass, RT-induced side effects such as ECM remodeling, vasculopathies and neuroinflammation are well documented that cause reduced neurogenecity and premature aging like complications during post-cancer survivorship. Since mesenchymal stromal cells (MSCs) are multipotent adult stem cells that support tissue integrity, homeostasis and repair through factors they release, we here investigated the potential of iPSC-derived MSC (iMSC)-secretome in immunomodulation and vasculature repair in response to radiation-induced alterations utilizing models of human monocytic and microglial cells (THP1, HMC-3) and human brain endothelial cells (HCMEC/D3). Approaches: (a) Investigate the impact of iMSC secretome on vasculature damage caused by radiation-induced cell injury and RT-induced inflammation, by evaluating its effects on (i) endothelial cell survival and morphogenesis (ii) activation of peripheral monocytes stimulated by X-ray radiation therapy (RT), RT-induced microglial injury, and vasculature injury mediated inflammation (b) Identify factors and pathways that may contribute to the observed phenotype. Results: Decline in intact angiogenic tube formation and less compact spheroid formation was observed for HCMEC/D3 cells after irradiation at doses (Gy): 2.5, 5, 10, 15, and 30, with maximal effect observed at 30Gy. Evaluating the effects of iMSC secretome on radiation induced endothelial cell damage and inflammation revealed increased cell viability with reduced apoptosis, higher cell adherance and better spheroid compactness in 5Gy irradiated HCMEC/D3 cells after iMSC-conditioned media (iMSC-CM) treatment. Reduction in NFκB promoter activity was observed in irradiated THP1- NFκB-Luc2 reporter line, with reduced levels of TNF-α release per unit cell viability in THP1 after iMSC-CM treatment. NFκB promoter activity was also reduced in effect of iMSC treatment in THP1- NFκB-Luc2 reporter cells subjected to irradiated vasculature cells (D3), with or without iMSC coculture and, irradiated microglial cells (HMC3), mimicking vasculature injury, microglial injury, and immune cell crosstalk, respectively. iMSC secretome facilitated a more networked tube formation in HCMEC/D3 cells in coculture of D3+iMSC cells that was longer retained. Cytokine arrays revealed iMSC-CM to have proangiogenic, immunomodulatory (immune suppressive) and chemotactic factors: MCP1, ANG (angiogenin), IL6, IL8, GRO, GROα, RANTES, and SDF1. Our initial pathway analysis using human phospho-proteome profiling showed iMSC secretome elevates levels of beta-catenin, and PRAS40 (AKT/mTOR modulator) and lowers level of pRSK1/2/3 in HCMEC/D3. Conclusions: Taken together, we demonstrated that iMSC-secretome complements the proangiogenic and immunosuppressive effects of iMSC during radiation induced injury. Further studies are required to validate the in vivo potential of iMSC-secretome as safe biological therapy in long-term cancer survivors. Citation Format: Kshama Gupta, Ralph B. Perkerson III, Tammee M Parsons, Prasanna Vibhute, Abba C. Zubair, Alfredo Quinones-Hinojosa, Takahisa Kanekiyo. Impact of human iPSC-derived MSC secretome in modulating radiation induced inflammation and brain vascular endothelial cell damage [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C116.

Transient global amnesia (TGA) is a neurological condition characterized by temporary memory loss and classically associated with a reversible unilateral punctate focus of restricted diffusion in the cornu ammonis 1 (CA1) region of the hippocampus. Historically, the lesions were considered to be transient in nature with no long-term imaging abnormality. However, more recent studies have challenged the concept that there are no long-term neurological sequelae. In line with this evidence, we explore the role of ultra-high-resolution imaging using 7 Tesla MRI to evaluate for long-term imaging abnormalities in a 63-year-old woman with a typical clinical course and acute TGA imaging findings. The 7 Tesla MRI revealed a residual lesion on susceptibility-weighted imaging (SWI) with evidence of gliosis and volume loss at the site of the acute lesion in CA1 eight months after the acute episode. This case challenges the traditional mantra of TGA as a fully reversible condition with no long-term imaging findings, suggesting the need for further research using ultra-high-field MRI to determine TGA's potential long-term imaging sequelae and any association with neurocognitive sequelae.

Transient ischemic attack (TIA) has gained significant attention recently due to the increased incidence of subsequent stroke. However, there are many nonvascular clinical mimics of TIA, creating a need for improved biomarkers to identify a vascular origin. Following the recent approval of ultra-high field (UHF) 7T MRI in clinical practice, several clinical studies have highlighted its added utility in neuroimaging compared to lower-field 1.5T and 3T MRI, particularly in epilepsy and multiple sclerosis. Our case series of three patients with TIA illustrates that 7T MRI can depict small areas of intracortical microhemorrhages and microinfarctions, which could not be resolved with 3T or 1.5T MRI. There are currently no reports of intracortical localization of microhemorrhages in patients with TIA. This discovery may enhance our understanding and characterization of cerebrovascular abnormalities in TIAs. In addition, UHF imaging could potentially be utilized to distinguish transient neurological episodes secondary to cerebrovascular events from other differential considerations. Our cases highlight the underestimation of imaging abnormalities in cases of TIA and support the potential expanded application of clinical 7T to assess patients with TIA. Future studies are necessary at 7T redundant to determine the true incidence of such lesions in TIA and to examine the correlation between cortical microhemorrhages and subsequent ischemic stroke, hemorrhagic events, and neurocognitive impairment.

Objective Schwannomas are common nerve sheath tumors and may occur anywhere in the body. 4% of head and neck schwannomas occur in the sinonasal cavity, and fewer yet have an intracranial component, making these presentations extremely rare. Furthermore, schwannomas present with nonspecific imaging signs and can only be definitively differentiated via histopathologic review, leading to misdiagnosis as various nasal tumors. We aim to conduct a review of published literature on sinonasal schwannomas with and without intracranial extension and provide additional case representations. Methods A literature review was conducted using the PubMed Database with the terms “sinonasal schwannoma,” “intracranial,” “anterior skull base,” and “schwannoma.” Results were reviewed, and additional cases identified were referenced and included in the study. Inclusion criteria were any case with intracranial extension of the schwannoma. There were no exclusion criteria. Review data was compiled into Excel and used for data analysis and comparison. Additionally, a search was done within our institution to identify additional cases of sinonasal schwannoma. Results We identified 17 cases of sinonasal schwannoma with intracranial extension, five from our institution and twelve from literature. Analysis revealed: 8 females (47%), 9 males (53%), 9 patients presented with headaches (53%), 6 patients presented with anosmia (35%), 4 patients presented with nasal obstruction (24%), and 2 patients with no symptoms (12%). Mean age and median were 39.4 ± 10.1 and 40, respectively. For treatment, 4 patients underwent endoscopic resection (24%), 11 underwent craniotomy (65%), and data was unavailable for 2 patients. Post-treatment complications occurred in 6 patients, 5 had CSF leaks (29%) and 1 had a hematoma (6%). Conclusion We identified and discussed 17 cases of sinonasal schwannoma with intracranial extension. We hope our review provides insight for clinicians to maintain schwannoma as a potential differential when evaluating nasal and anterior skull base masses.