Follow-up Brain MRI Research Articles

PATH-31. COMPLETE TUMOR DISAPPEARANCE ON BRAIN MRI AFTER STANDARD CHEMORADIATION THERAPY FOR A MOLECULAR GLIOBLASTOMA

Abstract INTRODUCTION Glioblastoma (GBM) is the most aggressive brain tumor. The WHO CNS5 classification has newly incorporated three molecular criteria in diagnosing molecular GBM, including a concurrent gain of chromosome 7 and loss of chromosome 10 (+7/-10), TERT promoter mutation, or EGFR amplification. Despite new classification, the Stupp protocol remains the standard of care for all GBMs. However, it is unclear if the treatment response of the molecular GBM with low grade features is the same as the limited response of the traditional histopathological GBM. CASE REPORT A 74-year-old male presented in August of 2023 with new onset left-sided facial numbness. The numbness resolved spontaneously that day. Brain MRI was notable for a diffuse left frontal T2/Flair hyperintense lesion extending across the corpus callosum into the right frontal lobe without definite enhancement. Brain biopsy from 8 sites of the tumor demonstrated a subset of areas with mild hyper-cellularity, suggesting a low-density infiltrating glioma. However, TERT promoter mutation (-124C>T), was detected along with wild-type IDH1, supporting molecular GBM. Studies also found unmethylated MGMT gene promotor. Brain MRIs after 3 and 6 months showed no tumor progression. The patient has remained asymptomatic apart from baseline mild forgetfulness. He was started on the 6-week standard concomitant temozolomide and radiation therapy. Follow-up brain MRI after the above treatment showed complete imaging resolution of the tumor. DISCUSSION It is very rare for complete imaging resolution of GBM on brain MRI after standard 6-week chemoradiation therapy. Our case suggests that molecular GBM with low-grade features on imagine and pathology might have a better response to the standard treatment than traditional histopathological GBM even though the molecular GBM patient has unfavorable prognostic factors such as unmethylated MGMT and older age (>70 years old). Our experience emphasizes the heterogenous response of molecular GBM to the current standard treatment.

NCMP-22. CO-OCCURRENCE OF MULTIPLE SCLEROSIS AND HODGKIN LYMPHOMA. IS THERE A COMMON PATHOPHYSIOLOGY?

Abstract BACKGROUND Multiple sclerosis (MS) and Hodgkin lymphoma (HL) share common epidemiology, genetics and immunological factors. Both affect immune activation, cell proliferation and lymphocyte-mediated immunity. However, occurrence of these two distinct clinical conditions is rare. We present a case of a woman with transverse myelitis fulfilling criteria for MS with synchronous HL. CASE REPORT A 37-year-old woman presented to the emergency room with bilateral leg weakness, numbness and urinary retention. A contrasted MRI of the brain and thoracic spine showed non-specific, non-enhancing white-matter lesions in the brain, and patchy areas of peripheral contrast-enhancement with T2-hyperintensity in the thoracic cord. Treatment with steroid infusion resulted in mild improvements of leg weakness and numbness. Cerebrospinal fluid (CSF) demonstrated oligoclonal bands (OCB) and increased IgG index. Serum was positive for JCV antibody. Due to the atypical MRI findings, namely the peripheral nature of thoracic contrast-enhancement, we were concerned for other inflammatory or autoimmune etiologies. A computed tomography of the chest, abdomen and pelvis revealed a large mediastinal mass and enlarged lymph nodes. A biopsy revealed classic HL. Three-months later, a follow-up MRI brain showed worsening contrast-enhanced lesions. A repeat CSF study revealed normal OCBs and IgG index. CSF was negative for malignant cells and JC virus DNA. To rule out a rare possibility of central nervous system HL, a biopsy of an enhancing brain lesion was obtained, which showed focal gliosis and focal perivascular lymphocytic infiltrates. No malignant cells were observed. She was diagnosed with multiple sclerosis and started systemic chemotherapy (doxorubicin, bleomycin, dacarbazine and vinblastine) for HL. CONCLUSIONS We report a case of an atypical transverse myelitis with HL. Although familial genetic clustering has been described, other potential common risk-factors between MS and HL are Epstein-Barr Virus infection and immunologic overlap, particularly in the context of lymphocyte-mediated immunity.

Adalimumab induced CNS demyelination in a patient with multiple pre-existing autoimmune diseases; treatment contemplation.

Anti-TNF agents like Adalimumab are safe and effective for rheumatologic disorders, but they have been reported to cause demyelinating diseases like Multiple Sclerosis (MS). A 47-year-old woman with left hand weakness was evaluated. She had a previous medical history of Intermediate Uveitis (IU) and Rheumatoid arthritis (RA). anti-TNF-α treatment was initiated with adalimumab two years before this visit. MRI showed numerous T2-hyperintense lesions in bilateral periventricular, juxtacortical, and subcortical areas, which were absent in her scan before anti-TNF therapy. She was diagnosed with MS, and Adalimumab was discontinued. IV glucocorticoids (GCs) were administered with marked improvement. She was then started on anti-CD20 therapy with Rituximab. A year later, she was symptom-free, and her follow-up Brain MRI showed no new lesions. The link between MS and TNF-α inhibitors is poorly understood, but several hypotheses have been proposed. Discontinuing anti-TNF therapy alone may not be enough to prevent further demyelinating disease activity, and it is essential to consider the necessity of starting a disease-modifying treatment. Autoimmunity plays a significant role in rheumatologic and neurological diseases, and as personalized medicine advances, understanding genetic risk is crucial for selecting appropriate therapeutic targets. A thorough evaluation of a patient's family background is recommended before therapeutic decision-making, especially in patients with multiple autoimmune disorders, and the question of whether TNF-α is a suitable therapeutic target in patients with multiple autoimmune disorders is raised.

Cerebral damage after malignant hypertensive crisis: cerebral MRI follow-up data

Abstract Background Malignant hypertension (MHT) crisis is characterized by acute and diffuse microvascular damages, and the brain is a primary target organ. While a recent MRI study has revealed extensive and frequent cerebral injuries during the acute phase of MHT crisis (1), there is a scarcity of follow-up data. Purpose This study aims to investigate the evolution of MRI markers of cerebral injury following the management of the acute phase of MHT. Methods In this retrospective analysis, we examined brain MRI data from patients admitted for acute MHT between 2008 and 2022 at our center. Eligible patients had at least one follow-up brain MRI available. A skilled operator conducted a comprehensive analysis of each brain MRI, searching for posterior reversible encephalopathy syndrome (PRES), acute stroke or cerebral hemorrhage and microangiopathy markers, blinded for clinical and demographical data. Results Among 149 patients enrolled, 104 had a brain MRI at inclusion, 47 individuals had at least one follow-up brain MRI and were included in the analysis. 72,3% were male, mean age was 48,2 ± 10.8 years and 45,7% presented blood pressure control at the time of the follow-up brain MRI. Median interval between initial and follow-up brain MRI was 228 (84 – 726) days. Five (10,6%) new recent strokes, 2 (4,3 %) cerebral hemorrhage and 0 PRES were recorded during follow-up. On the follow-up brain MRI, more patients presented chronic lacunar infarct and/or microbleeds, in higher numbers. On the contrary, overall Fazekas score was stable in 31 patients (66,0%), improved in 15 patients (31,9 %) and worsened in 1 patients (2,1%). Comparison of subgroups dichotomized according to blood pressure control or follow up duration showed no difference in brain MRI markers. Conclusion This study offers valuable insights into the risk of new cerebrovascular events and the evolution of brain MRI markers after managing the acute phase of MHT. Our findings emphasize the dynamic nature of cerebral microvascular burden and the potential for regression of white matter hyperintensities. A better understanding of these phenomena might contribute to improved diagnosis, tailored treatment, and proactive patient care in the context of MHT.

7392 Unilateral Adrenal Embolization In Cushing Disease-A Lifesaving Emergent Procedure

Abstract Disclosure: M. Sadiq: None. B. Irshad: None. A. Haider: None. Case presentation: A 59-year-old female was diagnosed with Cushing Disease (CD) thirteen years ago with symptomatic hypercortisolism. Hypokalemia and elevated 24-hour urine cortisol (392 ug/24 hr, n 0-50 ug/24 hr) were noted at the time of diagnosis. Following LDDST, morning cortisol was 30.5 ug/dl, and HDDST showed greater than 50% suppression. A pituitary macroadenoma with bilateral cavernous sinus extension was noted on MRI Sella. Due to cavernous sinus invasion, she was not considered a surgical candidate and underwent Gamma knife radiation. 24-hour urine cortisol decreased significantly (20 ug/24 hours). Two years follow-up MRI brain showed an empty Sella and AM cortisol was noted to be normal at 12.2 ug/ dl with no evidence of AI. She was lost to follow-up and reestablished almost ten years after her initial gamma knife and was symptomatic from hypercortisolism. 24-hour urine cortisol at 85.4 mcg/24 hr, abnormal salivary cortisol x 2 (0.24 and 0.20 mcg/dl n < 0.09 mcg/dl) confirming hypercortisolism. MRI of Sella showed recurrent adenoma with bilateral sellar masses. She was referred to Neurosurgery and was started on Ketoconazole and Paseriotide once-monthly injections. She developed new onset diastolic heart failure & upper GI bleeding, requiring hospitalization. High ACTH level of 668 pg/ml (n. 6.6- 65 pg/ ml). 8 am cortisol was 107.6 ug/dl which was suppressed to 16.1 after 8 mg overnight Decadron. Repeat Gamma knife was planned but due to her decline, it was decided to do unilateral adrenal artery embolization to reduce hypercortisolism. IR-guided adrenal artery embolization of the left middle & inferior adrenal arteries was performed. She required stress dosing of HC post-embolization which was tapered off while monitoring 8 am cortisol which started to rise & 24-hour cortisol levels were noted to be normal (51.2 mcg/24 H) on post-embolization day eight. Gamma knife radiation treatment was performed a month later after which she was noted to have GWS and required Hydrocortisone 15/10 mg twice daily, which she has been taking to date. 24-hour urine cortisol remains normal at 11.8 mcg/24 h. Discussion: Treatment for CD is primarily surgical. Radiotherapy is a second-line alternative in tumors that are non-amenable to surgery. Radiotherapy takes time to achieve its full effect. Cushing Disease patients with significant hypercortisolism and resultant complications require urgent treatment. Unilateral Adrenalectomy is described in literature to curb the cortisol burden . Similarly Unilateral Adrenal artery embolization offers less invasive approach to treat patients considered unfit for surgery. Conclusion: Unilateral adrenal artery embolization can be considered a bridging treatment in CD to reduce cortisol burden and improve the metabolic profile following which a more definitive treatment such as repeat surgery or radiotherapy can lead to long-term remission. Presentation: 6/1/2024

An unusual presentation of unilateral vagoglossopharyngeal neuralgia accompanied by unilateral accessory nerve palsy

BackgroundVago-glossopharyngeal neuralgia (VGN) is a rare condition characterized by neuropathic pain in the areas innervated by the glossopharyngeal and vagus nerve. Diagnosis can be challenging due to its rarity and the need to differentiate it from other sources of pain. Neurovascular conflicts involving the glossopharyngeal nerve and surrounding vasculature are often implicated in the development of VGN. Surgical interventions, such as microvascular decompression, have shown promise in relieving symptoms, but long-term outcomes remain poorly understood. This case report presents a unique manifestation of VGN accompanied by unilateral accessory nerve palsy and syncope, shedding light on the complexities involved in diagnosis and management.Case presentationThe presented case involves a 42-year-old patient without comorbidities with a 1-year history of syncope, dysphonia, cough, oropharyngeal pain, dysphagia, right periaricular pain, and weakness of the right sternocleidomastoid and trapezius muscle. After an initial evaluation, compression of the right cranial nerves IX, X, and XI by the posterior inferior cerebellar artery (PICA) was identified as the cause. The patient underwent microvascular decompression, which provided 3 years of symptom relief. However, symptoms recurred with additional manifestations, including left periauricular pain and increased syncopal episodes of cardiogenic origin. A follow-up brain MRI revealed compression of the left cranial nerves IX and X. A second surgical intervention targeting the left side resulted in partial improvement but symptom reappearance after 1 year. Finally, a third surgery involving the left side was performed, and along with isolating the affected cranial nerves, two superior rootlets of the vagus nerve were rhizotomized. Postoperative recovery was successful, with complete resolution of symptoms and no recurring issues during follow-up examinations.ConclusionThis case underscores the complexity of diagnosing and managing neurovascular conflicts associated with VGN pain syndrome. While initial microvascular decompression provided relief, the recurrence of symptoms and emergence of new manifestations highlight the challenges in managing this condition. Precise identification of nerve compression and targeted surgical interventions, such as sectioning the superior roots of the vagus nerve, offer potential efficacy in refractory cases. Further studies and long-term follow-up are necessary to gain comprehensive insights into the progression and outcomes of these interventions.

Stepwise Corrected Attention Registration Network for Preoperative and Follow-Up Magnetic Resonance Imaging of Glioma Patients.

The registration of preoperative and follow-up brain MRI, which is crucial in illustrating patients' responses to treatments and providing guidance for postoperative therapy, presents significant challenges. These challenges stem from the considerable deformation of brain tissue and the areas of non-correspondence due to surgical intervention and postoperative changes. We propose a stepwise corrected attention registration network grounded in convolutional neural networks (CNNs). This methodology leverages preoperative and follow-up MRI scans as fixed images and moving images, respectively, and employs a multi-level registration strategy that establishes a precise and holistic correspondence between images, from coarse to fine. Furthermore, our model introduces a corrected attention module into the multi-level registration network that can generate an attention map at the local level through the deformation fields of the upper-level registration network and pathological areas of preoperative images segmented by a mature algorithm in BraTS, serving to strengthen the registration accuracy of non-correspondence areas. A comparison between our scheme and the leading approach identified in the MICCAI's BraTS-Reg challenge indicates a 7.5% enhancement in the target registration error (TRE) metric and improved visualization of non-correspondence areas. These results illustrate the better performance of our stepwise corrected attention registration network in not only enhancing the registration accuracy but also achieving a more logical representation of non-correspondence areas. Thus, this work contributes significantly to the optimization of the registration of brain MRI between preoperative and follow-up scans.

Primary diffuse large B-cell lymphoma of the central nervous system identified with CSF biomarkers

BackgroundDiagnosis of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is challenging and often delayed. MRI imaging, CSF cytology and flow cytometry have a low sensitivity and even brain biopsies can be misleading. We report three cases of PCNSL with various clinical presentation and radiological findings where the diagnosis was suggested by novel CSF biomarkers and subsequently confirmed by brain biopsy or autopsy.Case presentations.The first case is a 79-year-old man with severe neurocognitive dysfunction and static ataxia evolving over 5 months. Brain MRI revealed a nodular ventriculitis. An open brain biopsy was inconclusive. The second case is a 60-year-old woman with progressive sensory symptoms in all four limbs, evolving over 1 year. Brain and spinal MRI revealed asymmetric T2 hyperintensities of the corpus callosum, corona radiata and corticospinal tracts. The third case is a 72-year-old man recently diagnosed with primary vitreoretinal lymphoma of the right eye. A follow-up brain MRI performed 4 months after symptom onset revealed a T2 hyperintense fronto-sagittal lesion, with gadolinium uptake and perilesional edema. In all three cases, CSF flow cytometry and cytology were negative. Mutation analysis on the CSF (either by digital PCR or by next generation sequencing) identified the MYD88 L265P hotspot mutation in all three cases. A B-cell clonality study, performed in case 1 and 2, identified a monoclonal rearrangement of the immunoglobulin light chain lambda (IGL) and kappa (IGK) gene. CSF CXCL-13 and IL-10 levels were high in all three cases, and IL-10/IL-6 ratio was high in two. Diagnosis of PCNSL was later confirmed by autopsy in case 1, and by brain biopsy in case 2 and 3.ConclusionsTaken together, 5 CSF biomarkers (IL-10, IL-10/IL-6 ratio, CXCL13, MYD88 mutation and monoclonal IG gene rearrangements) were strongly indicative of a PCNSL. Using innovative CSF biomarkers can be sensitive and complementary to traditional CSF analysis and brain biopsy in the diagnosis of PCNSL, potentially allowing for earlier diagnosis and treatment.

Validating Brain Tumor Reporting and Data System (BT-RADS) as a Diagnostic Tool for Glioma Follow-Up after Surgery.

Gliomas are a type of brain tumor that requires accurate monitoring for progression following surgery. The Brain Tumor Reporting and Data System (BT-RADS) has emerged as a potential tool for improving diagnostic accuracy and reducing the need for repeated operations. This prospective multicenter study aimed to evaluate the diagnostic accuracy and reliability of BT-RADS in predicting tumor progression (TP) in postoperative glioma patients and evaluate its acceptance in clinical practice. The study enrolled patients with a history of partial or complete resection of high-grade glioma. All patients underwent two consecutive follow-up brain MRI examinations. Five neuroradiologists independently evaluated the MRI examinations using the BT-RADS. The diagnostic accuracy of the BT-RADS for predicting TP was calculated using histopathology after reoperation and clinical and imaging follow-up as reference standards. Reliability based on inter-reader agreement (IRA) was assessed using kappa statistics. Reader acceptance was evaluated using a short survey. The final analysis included 73 patients (male, 67.1%; female, 32.9%; mean age, 43.2 ± 12.9 years; age range, 31-67 years); 47.9% showed TP, and 52.1% showed no TP. According to readers, TP was observed in 25-41.7% of BT-3a, 61.5-88.9% of BT-3b, 75-90.9% of BT-3c, and 91.7-100% of BT-RADS-4. Considering >BT-RADS-3a as a cutoff value for TP, the sensitivity, specificity, and accuracy of the BT-RADS were 68.6-85.7%, 84.2-92.1%, and 78.1-86.3%, respectively, according to the reader. The overall IRA was good (κ = 0.75) for the final BT-RADS classification and very good for detecting new lesions (κ = 0.89). The readers completely agreed with the statement "the application of the BT-RADS should be encouraged" (score = 25). The BT-RADS has good diagnostic accuracy and reliability for predicting TP in postoperative glioma patients. However, BT-RADS 3 needs further improvements to increase its diagnostic accuracy.

18 F-MFBG PET/CT and MRI in Identifying Brain Metastases in a Posttreatment Neuroblastoma Patient.

A 7-year-old girl with known brain metastasis from neuroblastoma developed new onset of severe headache. A brain MRI confirmed known metastasis in the right frontal lobe of the brain without new abnormalities. The patient was enrolled in a clinical trial using 18 F-MFBG PET/CT to evaluate patients with neuroblastoma. The images confirmed abnormal activity in the known lesion in the right frontal lobe. In addition, the PET showed additional foci of abnormal activity in the left cerebellopontine region. A follow-up brain MRI study acquired 4 months later revealed abnormal signals in the same region.

Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial

People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19). Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 16·8 (90·2% CI 14·5-19·1) for placebo, 16·7 (14·8-18·6) for 25 mg milvexian once daily, 16·6 (14·8-18·3) for 25 mg twice daily, 15·6 (13·9-17·5) for 50 mg twice daily, 15·4 (13·4-17·6) for 100 mg twice daily, and 15·3 (12·8-19·7) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 0·99 (90·2% CI 0·91-1·05) for 25 mg once daily, 0·99 (0·87-1·11) for 25 mg twice daily, 0·93 (0·78-1·11) for 50 mg twice daily, 0·92 (0·75-1·13) for 100 mg twice daily, and 0·91 (0·72-1·26) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator. Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA. Bristol Myers Squibb and Janssen Research & Development.

THU018 Remarkable Response Of ACTH-secreting Pituitary Carcinoma To Immune Checkpoint Inhibitors: A Case Report

Abstract Disclosure: J. Park: None. W. Choi: None. A. Hong: None. J. Yoon: None. H. Kim: None. H. Kang: None. Background: ACTH-secreting pituitary carcinoma transformed from Cushing’s disease is very rare and has aggressive characteristics with limited treatment options. We report a case of ACTH-secreting pituitary carcinoma patient who showed a excellent response to immune checkpoint inhibitors (ICIs). Clinical Case: A 70-year-old female presented with a rapidly growing pituitary carcinoma transformed from Cushing’s disease after bilateral adrenalectomy. Her tumor initially responded to 6 cycles of temozolomide and 7 cycles of temozolomide plus capecitabine. However, multiple brain and pulmonary metastases were newly seen on following imaging studies and the patient had worsening generalized pigmentation on her whole body with newly developed headache, diplopia, and ptosis of the left eye. After introduction of three cycles of ipilimumab plus nivolumab therapy, her plasma ACTH level decreased dramatically from 58,000 pg/ml to 198 pg/ml with improving skin pigmentation and headache episodes. We maintained nivolumab and observed that the plasma ACTH level be normalized to 44 pg/ml (normal range: 6 – 60 pg/ml). Her follow-up brain MRI and chest CT scan also showed marked response, some of the chest lesions even showed nearly complete response (figure 1). On the last follow-up visit, we confirmed that she was in good general condition and tolerable to nivolumab maintenance therapy with glucocorticoid replacement. Conclusion: Immune checkpoint inhibitors (ICIs) may be effective therapeutic options in aggressive pituitary carcinoma and can be considered in temozolomide resistant cases. Moreover, because of the excessively high cost, we emphasize the necessity of clinical trials of ICIs for rare diseases like pituitary carcinomas to expand insurance coverage and reduce the unmet needs of medical care.

Pattern of Brain Parenchymal Damage Related to Cerebral Small Vessel Disease in Carriers of Rare NOTCH3 Variants.

Previous studies reported that carriers of rare NOTCH3 variants comprised more than 10% of the general population and are susceptible to a heavy overall burden of cerebral small vessel disease while the injury patterns remain uncovered. This study aimed to investigate the imaging features in relation to rare NOTCH3 variants and the interaction between cortical atrophy and white matter lesions from a longitudinal view, with respect to spatial and dynamic patterns. As part of a community-based cohort, we included participants with complete whole-exome sequencing and brain MRI in the baseline analysis. All participants were invited for a 5-year follow-up MRI, and those who did not complete the follow-up were excluded from the longitudinal analysis. NOTCH3 variants with minor allele frequency <1% in all 4 public population databases were defined as rare variants. We used general linear models to compare the volume of white matter hyperintensity (WMH) volume and brain parenchymal fraction between rare NOTCH3 variant carriers and noncarriers. In addition, we compared the WMH probability map and vertex-wise cortex maps at a voxel/vertex-wise level. A total of 1,054 participants were included in baseline analysis (13.56% carried rare NOTCH3 variants), among whom 661 had a follow-up brain MRI (13.76% carried rare NOTCH3 variants). Rare NOTCH3 variant carriers had a heavier white matter hyperintensity burden (1.65 vs 0.85 mL, p = 0.025) and had more extensive WMH distributed in the periventricular areas. We also found that rare NOTCH3 variant carriers were susceptible to worse cortical atrophy (β = -0.004, SE = 0.002, p = 0.057, adjusted for age and sex). Cortical atrophy of multiple regions in the frontal and parietal lobes was related to white matter hyperintensity progression. Individuals with rare NOTCH3 variants have a distinct pattern of brain parenchymal damage related to CSVD. Our findings uncover the important genetic predisposition in age-related cerebral small vessel disease in the general population.

SDPS-09 MIXED RESPONSE OF BRAIN METASTASES TREATED WITH OSIMERTINIB PREDICTS INFERIOR SURVIVAL OUTCOMES: AN ARTIFICIAL INTELLIGENCE-BASED LESION-LEVEL ASSESSMENT FOR CRANIAL CONTROL OF EGFRMUTANT NONSMALL CELL LUNG CANCER

Abstract Osimertinib has been found to be effective for intracranial control in patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). However, the lesion-level response of brain metastases to osimertinib has not been thoroughly evaluated. This retrospective study included 73 patients with EGFR-mutant NSCLC and brain metastases who were treated with osimertinib at a single institution from 2016 to 2021. Patients with the leptomeningeal disease were excluded. The study used an FDA-approved brain tumor management artificial intelligence (AI) platform, VBrain, to identify, track, and measure brain metastases on the baseline and follow-up MRI brain scans. Mixed response (MiR) was defined as the occurrence of progressive or new lesions along with synchronous responsive shrinking intracranial lesions at the first follow-up scan. K-means grouping was used to partition patients into two clusters according to their response heterogeneity. With a median follow-up of 23.8 months, a high MiR score (higher than 103%, n=25) was associated with worse cranial-progression-free survival (3.2 vs. 17.9 months, p&amp;lt;0.0001) and significantly inferior overall survival (12.4 vs. 30.1 months, HR=2.35, p=0.016). This poses a similar negative impact on the survivals of 18 patients with pure RANO-BM progression (HR=2.52, p=0.025). Eight patients had the highest MiR score (MiRmax), in whom synchronous new lesions and completely responsive tumors were observed. In a multivariate Cox proportional-hazards regression involving performance status, extracranial failure, tumor volume, lesion number, and RANO-BM classification as variables, MiRmax remained an independent prognosticator for inferior survival (HR=5.20, 95%CI; 2.21–12.23, p=0.002). Our study demonstrates that MiR in brain metastases from EGFR-mutant NSCLC treated with osimertinib is associated with inferior survival outcomes and a higher risk of local progression. Lesion-level response assessment using AI may provide important prognostic information and aid in treatment decision-making for these patients.

Systemic immune-inflammation index and progression of white matter hyperintensities of presumed vascular origin. A longitudinal population study in community-dwelling older adults living in rural Ecuador

BackgroundInformation on the association between the systemic immune-inflammation index (SII) and white matter hyperintensities (WMH) of presumed vascular origin is confined to cross-sectional studies. We sought to evaluate the impact of SII on WMH progression in community-dwelling older adults. MethodsFollowing a longitudinal prospective study design, participants of a population-based cohort received baseline blood tests to calculate the SII (platelets x neutrophils / lymphocytes x 109 L) together with clinical interviews and brain MRIs. Participants with follow-up brain MRI were included in the analysis. Poisson regression models adjusted for demographics and cardiovascular risk factors were fitted to assess the incidence rate ratio of WMH progression by levels of the SII. ResultsAcross 246 study participants (mean age: 65.5 ± 5.9 years; 55% women), the mean SII was 434.7 ± 193.8 × 109 L, and WMH progression was found in 101 (41%) individuals after a mean of 7.3 ± 1.5 years. A multivariate Poisson regression model showed increased WMH progression rate among individuals in the fourth quartile of the SII compared with those in the first quartile (IRR: 1.87; 95% C.I.: 1.02–3.41). ConclusionsStudy results provided novel evidence of an independent association between the SII and WMH progression. The SII may be able to identify individuals at high risk of WMH progression.

Modified Nasoseptal Flap Technique to Prevent the Recurrence of Rathke's Cleft Cyst.

Rathke's cleft cysts (RCCs) are benign epithelial lesions arising from the Rathke's pouch remnants that fail to regress during embryogenesis. Some RCCs become symptomatic and require treatment. Cyst fenestration and drainage of its contents is the preferred procedure to treat symptomatic cases but carries a risk of recurrence. We propose the use of a novel modified nasoseptal flap technique to partially line the cyst wall to avoid recurrence. This was a prospective, observational study that included all RCC patients admitted to the Department of Neurosurgery, Aster Medcity, from April 2015 to May 2018. The modified nasoseptal flap technique was performed in all patients. They underwent preoperative and postoperative ophthalmological, endocrine, endoscopic, and MRI evaluations to look for recurrence. Ten patients underwent the modified nasoseptal flap technique. The median follow-up was 36 months. Postoperatively, all patients were relieved from headaches. Moreover, their visual fields and pituitary functions normalized. None of the patients developed recurrence of RCC on follow-up brain MRI. On endoscopic examination, all patients had retained patency of the fenestra. The longest follow-up was 72 months. The modified nasoseptal flap technique maintains patency and avoids recurrence of RCCs on long-term follow-up.

Single Cerebral Metastasis Mimicking Pyogenic Abscess in a Patient with Lung Adenocarcinoma.

HomeRadiology: Imaging CancerVol. 5, No. 3 Images in CancerFree AccessSingle Cerebral Metastasis Mimicking Pyogenic Abscess in a Patient with Lung AdenocarcinomaVíctor Pérez-Riverola , Olalla Vázquez Muiños, Mario Prenafeta Moreno, Roser Monmany Badia, Khalid El-Hamshari Rebollo, Esther Granell MorenoVíctor Pérez-Riverola , Olalla Vázquez Muiños, Mario Prenafeta Moreno, Roser Monmany Badia, Khalid El-Hamshari Rebollo, Esther Granell MorenoAuthor AffiliationsFrom the Department of Neuroradiology, UDIAT-CD, Hospital Universitari Parc Taulí, Parc del Taulí 1, 08208 Sabadell, Spain.Address correspondence to V.P.R. (email: [email protected]).Víctor Pérez-Riverola Olalla Vázquez MuiñosMario Prenafeta MorenoRoser Monmany BadiaKhalid El-Hamshari RebolloEsther Granell MorenoPublished Online:Apr 7 2023https://doi.org/10.1148/rycan.230004MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In As clinical signs of infection are often absent in patients with pyogenic abscesses, differential diagnosis with cerebral metastases is based on MRI findings.However, both entities often manifest as ring-enhancing lesions. Pyogenic brain abscesses usually show restricted diffusion in the lesion core and the dual-rim sign at susceptibility-weighted imaging. The dual-rim sign consists of two concentric rims bordering the lesion: a complete, smooth outer hypointense rim representing the fibrocollagenous capsular wall and an inner hyperintense rim representing a zone of granulation tissue (1). At perfusion imaging, the capsule of a cerebral abscess has a lower relative cerebral blood volume than the necrotic or cystic peripheral wall of a tumor due to microvessel angiogenesis by the tumor (2).Some cerebral metastases also show restricted diffusion, which does not correlate with the histologic type of the primary cancer (3). Proposed mechanisms for restricted diffusion in metastases include intracellular edema in viable tumor cells during transition to complete liquefactive necrosis (4) and a highly viscous mucin concentration (5).Key findings that help distinguish these atypical metastases from pyogenic abscess include high peripheral wall relative cerebral blood volume and absence of the dual-rim sign (Figure).Brain MR images in a 37-year-old male patient, a heavy tobacco and cannabis smoker, after a first seizure. (A) Contrast-enhanced T1-weighted MR image shows a smooth, ring-enhancing nodular right frontal lobe lesion surrounded by abundant vasogenic edema. (B, C) On diffusion-weighted images, the central core shows restricted diffusion. (D) On susceptibility-weighted image, a hypointense smooth ring completely surrounds the lesion, simulating a capsule. (E) The relative cerebral blood volume of the lesion’s peripheral wall (arrows) is high (mean relative cerebral blood volume ratio: 7.61 ± 2.70 [SD]). Chest CT findings (not shown) detected a cavitary pulmonary mass. Tests for tuberculosis and bronchoalveolar lavage fluid analysis were negative. Chest CT findings were initially misinterpreted as an infectious process. Follow-up brain MRI 8 weeks after starting antibiotics showed enlargement of the frontal lobe lesion, new ring-enhancing cerebral and cerebellar lesions, and signs of leptomeningeal carcinomatosis in the posterior fossa. The patient was diagnosed with lung adenocarcinoma following lung lesion biopsy.Download as PowerPointOpen in Image Viewer Disclosures of conflicts of interest: V.P.R. No relevant relationships. O.V.M. No relevant relationships. M.P.M. No relevant relationships. R.M.B. No relevant relationships. K.E.H.R. No relevant relationships. E.G.M. No relevant relationships.Keywords: MRI, MR-Diffusion-weighted Imaging, MR-Perfusion, Metastasis, Neuro-oncology, Lung Adenocarcinoma, Pyogenic AbscessAuthors declared no funding for this work.

Recanalized paramedian thalamoperforators after intraarterial tirofiban treatment in a patient with bilateral fetal-type PCAs (P8-5.028)

<h3>Objective:</h3> NA <h3>Background:</h3> There are increasing evidence that support the treatment effect of intraarterial tirofiban during endovascular thrombectomy in acute ischemic stroke. Here, we report a patient with bilateral fetal-type PCAs, whose paramedian perforating thalamic-mesencephalic arteries were recanalized after intraarterial tirofiban treatment during thrombectomy. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 78-year-old woman presented to the emergency room with acute onset of drowsy mentality, gaze palsy and quadriplegia (NIHSS 9). She had a history of hypertension and diabetes. Brain CT scan revealed no definite early ischemic damage and CTA showed steno-occlusion at the left distal VA and bilateral fetal type PCAs. Brain perfusion CT showed perfusion delay in posterior circulation territory. Under local anesthesia, an 6F Envoy^® catheter (Codman) was placed in the left distal VA of distal V2 segment. The angiography revealed the distal VA occlusion (V4 segment) (Fig. 1A). Suction thrombectomy was performed twice using 5F Sofia^® catheter (Microvention), and no clot was extracted (Fig. 1B). Recanalization of left distal VA with underlying severe ICAS at the occlusion site (Fig. 1C). Delayed angiogram showed subtle re-occlusion tendency of left distal VA, 0.5mg of intraarterial tirofiban was injected. Successful recanalization (mTICI 2C) with further recanalized paramedian perforating thalamic-mesencephalic arteries on distal BA after SCA branches was achieved (Fig. 1D). Follow-up brain MRI showed acute infarction at the posterior circulation territory including bilateral thalami. MRA showed patent left distal VA with underlying severe ICAS, and vessel wall MRI showed eccentric wall thickening without contrast enhancement or plaque hemorrhage. The patient recovered well at 1 week (NIHSS 0). <h3>Conclusions:</h3> In a patient with bilateral fetal type PCAs, distal BA could end after SCA branches and this site should be evaluated cautiously, because thalamoperforators could originate. Intraarterial tirofiban could be helpful to recanalize perforating arteries during thrombectomy. <b>Disclosure:</b> Dr. Baik has nothing to disclose.

Abstract Number ‐ 224: Stroke Mimic—Patient with Symptomatic Amyloid‐Related Imaging Abnormalities Presenting with Stroke‐like Symptoms.

Introduction Amyloid‐related imaging abnormalities (ARIA) are rare phenomena in patients taking monoclonal antibodies directed against amyloid beta in Alzheimer’s disease clinical trials. The pathogenesis is unclear, but may be due to an induced inflammatory microangiopathy. While the majority of cases are asymptomatic and resolve without intervention, a small subset can experience symptoms of sudden or uncertain onset. Given the relative rarity of this phenomena and the striking imaging findings, ARIA can be misdiagnosed as ischemic stroke or primary microangiopathy when presenting with acute‐subacute symptoms. Following diagnosis there is no clinical consensus on the optimal management and approaches range from withdrawal of the study drug to pulse‐dose steroids. Methods We present a case study of a patient admitted to our inpatient stroke service after 4 days of rapidly progressive confusion and sudden vision loss with MRI workup reporting subacute stroke. The findings were ultimately determined to be secondary to ARIA. Results A 67‐year‐old man with early onset Alzheimer’s disease enrolled in a clinical trial for donamemab presented with four days of marked cognitive decline including increased forgetfulness, confusion, and episodic hallucinations following an episode of abrupt vision loss. An outpatient MRI brain demonstrated subcortical hyperintensity that was initially reported as a subacute left occipital stroke. Notably, an MRI performed 3 months prior showed no abnormality. Neurological exam was remarkable for right superior quadrantanopia, memory impairment, and mild confabulation. Repeat MRI demonstrated FLAIR white matter hyperintensities and extensive susceptibility artifact in the left parieto‐occipital lobe, consistent with an inflammatory cerebral amyloid angiopathy (or ARIA). Spot EEG demonstrated no associated epileptiform discharges. Patient was treated with 7‐day course of IV Solumedrol and had improvement in visual symptoms. He was discharged on a prednisone taper and a followup MRI brain 4 weeks later showed near‐ complete resolution of the previously noted subcortical white matter changes. Conclusions ARIA can be seen in patients receiving anti‐amyloid monoclonal antibody treatments. Surveillance MRIs have been implemented to screen for such cases as a minority of patients with ARIA present with symptoms. As noted with this case study, a relatively acute presentation and imaging characteristics can lead to an initial misdiagnosis as subacute ischemic stroke. Vascular neurologists should be aware of this clinical entity, noting the natural history and treatment are not well established. This patient was treated aggressively as an inflammatory cerebral amyloid angiopathy with IV steroids and noted positive outcome. More research is required to establish the optimal acute medical management of patients with ARIA.

Spontaneous Near-Resolution of a Rathke’s Cleft Cyst

•Spontaneous near resolution of Rathke’s cleft cyst can occur•Conservative approach is recommended in the absence of mass effect or visual disturbance•The mechanism of spontaneous near resolution of RCC is poorly understood A 70-year-old Caucasian woman with history of chronic sinusitis presented to the Emergency department with 2-week history of headaches. Her physical examination was unremarkable including absence of galactorrhea, abnormal hair growth, or skin changes. Neurologic exam including visual fields were normal. Brain MRI revealed a 1.2 x 1.4x 1.3 cm ovoid, non-enhancing, cyst-like lesion with intrasellar and suprasellar components (Figure 1) with slight elevation and splaying of the optic chiasm and depression of the sella floor. Hormonal testing revealed normal values (Table 1). A conservative approach was chosen given the patient’s age, the lesion size, and lack of visual compromise or hormonal dysfunction.Table 1HormoneResultNormal RangeTSH0.90.280 – 3.980 ng/dlFree T40.600.58-1.64 ng/dlIGF-13741-279 ng/mlGrowth Hormone0.9<7.1 ng/mlProlactin19.272.74-19.64 ng/mLCortisol16.67-9a.m 4.0-22.0 mcg/dl Open table in a new tab At 1 month follow up she denied new symptoms. Repeat hormonal panel revealed a low FT4 0.5, and normal TSH 3.93, which prompted initiation of levothyroxine. The rest of the panel remained normal. A follow-up brain MRI revealed a hypoenhancing lesion within the sella with suprasellar extension measuring 1.1x 1.3 x0.9 cm (figure 2), contacting the optic chiasm without displacement. Ophthalmology evaluation reported normal visual fields. Neurosurgery recommended medical management. A year after initial presentation, TSH and Ft4 were normal on levothyroxine. Brain MRI revealed complete resolution of the previously characterized cystic lesion, with a normal-sized and shaped pituitary gland (figure 3). Patient continued to have intermittent headaches that were attributed to chronic sinusitis. The patient has not returned for a follow up visit, and we have been unable to reassess her pituitary/thyroid axis. What is the diagnosis? Answer: The clinical course and imaging findings are best explained by a rare case of a Rathke’s Cleft Cyst (RCC), with near spontaneous resolution. RCC are remnants of a failed regression of the developmental ectodermal pouch, characterized by unpredictable natural histories that can include spontaneous enlargement or less commonly decrease in size. The latter has been observed in up to 15% in studies evaluating the evolution and volumetry analysis of RCC (1Barkhoudarian G. Palejwala S.K. Ansari S. Eisenberg A.A. Huang X. Griffiths C.F. et al.Rathke’s cleft cysts: a 6-year experience of surgery vs. observation with comparative volumetric analysis.Pituitary [Internet]. 2019; 22 (Available from:): 362-371https://doi.org/10.1007/s11102-019-00962-yCrossref PubMed Scopus (19) Google Scholar). Symptoms may include headaches, pituitary dysfunction, and visual deficits from mass effect (2Altuwaijri N, Cote DJ, Lamba N, Albenayan W, Ren SP, Zaghloul I, et al. Headache Resolution After Rathke Cleft Cyst Resection: A Meta-Analysis. World Neurosurg [Internet]. 2018;111:e764–72. Available from: https://doi.org/10.1016/j.wneu.2017.12.170Google Scholar). There are no standardized management guidelines, however a conservative approach is preferred when there is absence of mass effect or visual disturbance as seen here(3Truong L.U.F. Bazin C. Gomis P. Decoudier B. Delemer B. Litré C.F. Surgery versus conservative care for Rathke’s cleft cyst.Neurochirurgie. 2021; 67: 104-111Crossref PubMed Scopus (4) Google Scholar). The mechanism of spontaneous resolution of RCC is poorly understood. This is a rare case of spontaneous near resolution of RCC in a patient that was followed by conservative therapy with regular clinical and radiologic follow up.