Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results.

Recurrent glioblastoma (rGBM) remains a major unmet medical need, with a median overall survival of less than 1 year. Here we report the first six patients with rGBM treated in a phase 1 trial of intrathecally delivered bivalent chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor (EGFR) and interleukin-13 receptor alpha 2 (IL13Rα2). The study's primary endpoints were safety and determination of the maximum tolerated dose. Secondary endpoints reported in this interim analysis include the frequency of manufacturing failures and objective radiographic response (ORR) according to modified Response Assessment in Neuro-Oncology criteria. All six patients had progressive, multifocal disease at the time of treatment. In both dose level 1 (1 ×107 cells; n = 3) and dose level 2 (2.5 × 107 cells; n = 3), administration of CART-EGFR-IL13Rα2 cells was associated with early-onset neurotoxicity, most consistent with immune effector cell-associated neurotoxicity syndrome (ICANS), and managed with high-dose dexamethasone and anakinra (anti-IL1R). One patient in dose level 2 experienced a dose-limiting toxicity (grade 3 anorexia, generalized muscle weakness and fatigue). Reductions in enhancement and tumor size at early magnetic resonance imaging timepoints were observed in all six patients; however, none met criteria for ORR. In exploratory endpoint analyses, substantial CAR T cell abundance and cytokine release in the cerebrospinal fluid were detected in all six patients. Taken together, these first-in-human data demonstrate the preliminary safety and bioactivity of CART-EGFR-IL13Rα2 cells in rGBM. An encouraging early efficacy signal was also detected and requires confirmation with additional patients and longer follow-up time. ClinicalTrials.gov identifier: NCT05168423 .

Case report of a giant cell tumor of the carotid sheath.

Giant cell tumor of the soft tissue (GCTST) is a neoplasm with low malignant potential and typically affects the trunk and extremities. Herein, we present a case of a palpable right neck mass diagnosed as a GCTST of the carotid sheath in a 38-year-old woman. A review of the imaging characteristics as well as of the differential diagnoses of primary neoplasms of the carotid space is presented.

Giant Iliac Artery Pseudoaneurysm Mimicking Postoperative Fluid Collection and Diskitis.

BACKGROUND: In this report, we describe an extremely rare case of a giant pseudoaneurysm of the internal iliac artery causing marked destructive changes at a disk space and mimicking diskitis-osteomyelitis. Only 2 other cases of pseudoaneurysms extending into the disk space have been reported, and those arose from the aorta and were relatively straightforward to diagnose. CASE DESCRIPTION: Our case is unique because the pseudoaneurysm arose from the internal iliac artery, an artery that is not usually included in the field of view of lumbar magnetic resonance imaging or computed tomography. However, the pseudoaneurysm was so large that it extended to the lumbosacral junction, where it eroded a disk space and caused findings of diskitis-osteomyelitis. CONCLUSIONS: Complex paraspinal fluid collections causing osseous erosions should raise the possibility of an aneurysm/pseudoaneurysm. Computed tomography or conventional angiography should be considered if the question of a vascular mass/collection cannot be answered on conventional cross-sectional imaging, as inadvertent biopsy of a pseudoaneurysm can cause catastrophic bleeding.

Significance of the absent vertebral artery T2 flow void on cervical spine MRI in atraumatic patients without acute neurological symptoms.

PURPOSE: Loss of the T2 vertebral artery flow void can be an ominous sign in patients with trauma. However, the significance of an absent vertebral artery flow void is less clear when discovered incidentally in patients without trauma or acute neurological symptoms. The purpose of this study was to review retrospectively the results of additional imaging and clinical evaluation in atraumatic patients without acute neurological symptoms found to have an incidentally discovered absent vertebral artery flow void on magnetic resonance imaging. MATERIALS AND METHODS: An imaging database was reviewed for absent vertebral artery flow voids in atraumatic cervical spine magnetic resonance images. Imaging and long-term clinical follow-up were recorded. RESULTS: Fifty-four patients were included in the study. All patients had clinical follow-up and 22 patients (40% of cases) had vascular imaging follow-up. Nine patients had a hypoplastic but patent vertebral artery on follow-up vascular imaging, and no further action was taken. Ten patients had evidence of stenosis or occlusion of the vertebral artery on follow-up imaging, none with acute neurological symptoms or new symptoms/subsequent change in management during follow-up. Three additional patients had vertebral artery dissections on follow-up imaging, but all of them had acute neurological symptoms at the time of imaging and acute infarcts on current or subsequent magnetic resonance imaging. The other 32 patients had clinical follow-up and remained asymptomatic throughout the study period, without change in management. CONCLUSION: In the absence of trauma or acute neurological symptoms an absent vertebral artery flow void has a low likelihood of altering patient management.

Neurointerventional Radiology for the Aspiring Radiology Resident: Current State of the Field and Future Directions.

OBJECTIVE: The purposes of this study were to document recent trends in stroke intervention at a tertiary-care facility with a comprehensive stroke center and to analyze current procedure volumes and the employment of specialty providers in neurointerventional radiology (NIR). MATERIALS AND METHODS: Institutional trends in the volume of mechanical thrombectomy were analyzed on the basis of the number of patients who underwent mechanical thrombectomy from 2013 to 2017. To evaluate the current status of mechanical thrombectomy volumes in the United States, the number of patients in the Medicare fee-for-service database who underwent mechanical thrombectomy in 2016 was assessed. The specialty backgrounds of the various providers who performed mechanical thrombectomy were analyzed. Procedure volumes for intracranial stenting, embolization, and vertebral augmentation procedures were assessed. RESULTS: From 2013 to 2017, the total numbers of mechanical thrombectomy procedures for acute ischemic stroke were 19 in 2013 and 111 in 2017. The total volume of mechanical thrombectomy procedures in the Medicare fee-for-service population in 2016 was 7479. For intracranial endovascular procedures, 20,850 were performed in the U.S. Medicare population in 2015 and 22,511 in 2016. Radiologists performed 45% of procedures in 2016; neurosurgeons, 41%; and neurologists, 11%. When the total numbers of percutaneous brain and spine procedures were combined, radiologists performed 41%; neurosurgeons, 23%; and neurologists, 3%. In 2016, there were a total of 220 active NIR staff at the NIR programs with rotating residents or fellows. In these programs, 49% of staff members were neuroradiologists, 41% were neurosurgeons, and 10% were neurologists. Of the 72 NIR departments with confirmed rotating fellows or residents, 14 had only neuroradiologists on staff, six had only neurosurgeons, and one had only neurologists. CONCLUSION: Increasing radiology resident interest and participation in NIR should ensure a steady influx of radiologists into the field, continuing the strong tradition of radiology participation, leadership, and innovation in NIR.

Muslin Granuloma Mimicking Parenchymal Hematoma in Patient with Seizures 30 Years After Aneurysm Wrapping.

Muslin foreign body granulomas are a known complication of muslin aneurysm wrapping and have been associated with vision loss from optochiasmatic arachnoiditis. Muslin granulomas have also been confused with abscesses due to surrounding inflammatory changes. In this clinical image, we present a unique case of a muslin granuloma mimicking an intraparenchymal hematoma.

Cranial Nerve Schwannomas: Diagnostic Imaging Approach.

Schwannomas are benign nerve sheath tumors that may arise along the complex course of the cranial nerves (CNs), anywhere in the head and neck. Sound knowledge of the CN anatomy and imaging features of schwannomas is paramount for making the correct diagnosis. In this article, we review approaches to diagnosing CN schwannomas by describing their imaging characteristics and the associated clinical presentations. Relevant anatomic considerations are highlighted by using illustrative examples and key differential diagnoses categorized according to regions, which include the anterior skull base, orbit, cavernous sinus, basal cisterns, and neck. The clinical presentations associated with CN schwannomas vary and range from no symptoms to symptoms caused by mass effect or CN deficits. Individuals with the inherited disorder neurofibromatosis type 2 are predisposed to multiple schwannomas. When a lesion follows the course of a CN, the radiologist's roles are to confirm the imaging features of schwannoma and exclude appropriate differential considerations. The characteristic imaging features of CN schwannomas reflect their slow growth as benign neoplasms and include circumscribed margins, displacement of local structures, and smooth expansion of osseous foramina. These neoplasms exhibit various degrees of solid enhancement, often with internal cystic spaces on magnetic resonance (MR) and computed tomographic (CT) images and heterogeneous high signal intensity specifically on T2-weighted MR images. Clinical and/or imaging evidence of end-organ compromise of the involved CN may exist and aid in the identification of the nerve of origin. With a detailed understanding of the course of the CNs, the diagnostic features of CN schwannomas, and the correlation between these data and the associated clinical presentations of these tumors, the radiologist can have a key role in the diagnosis of CN schwannomas and the treatment planning for affected patients. (©)RSNA, 2016.

Orbital congestion complicating treatment of cerebral vascular anomalies.

BACKGROUND: The decision between conservative management and invasive treatment of juxtaorbital intracranial vascular anomalies can be challenging. Whereas arteriovenous malformations (AVMs) can lead to vision loss and are potentially life-threatening if they rupture, invasive endovascular and surgical procedures also carry risks. CASE DESCRIPTIONS: Two patients developed blinding orbital congestion soon after they were treated successfully for cerebral vascular anomalies. The first patient, a 36 year-old man, underwent partial embolization followed by resection of a congenital frontal-lobe AVM. The second patient, a 62 year-old woman, underwent embolization of a periorbital/skull base dural arteriovenous malformation. After intervention, both patients developed unilateral vision loss proptosis, chemosis, complete ophthalmoplegia, and increased intraocular pressure. The first patient suffered from acute orbital compartment syndrome in the absence of any acute localized hemorrhage or thrombosis. The second patient experienced refractory acute glaucoma from orbital congestion, secondary hyphema, and angle closure caused by superior ophthalmic vein and cavernous sinus thromboses. CONCLUSIONS: These cases highlight the potential for orbital congestion to worsen acutely after invasive treatment of juxtaorbital cerebral vascular anomalies and suggest diverse mechanisms of resultant visual and orbital compromise. The first case represents the first report of orbital compartment syndrome after resection of a congenital AVM.

Vertebral artery dissection and cerebral infarction in a patient with recurrent ovarian cancer receiving bevacizumab.

•Ovarian cancer patients receiving bevacizumab treatment can experience significant adverse events.•We report a case of vertebral artery dissection associated with bevacizumab treatment.

An approach to comparing accuracies of two FLAIR MR sequences in the detection of multiple sclerosis lesions in the brain in the absence of gold standard.

RATIONALE AND OBJECTIVES: The purpose of this study was to present a new methodology to compare accuracies of two imaging fluid attenuated inversion recovery (FLAIR) magnetic resonance sequences in detection of multiple sclerosis (MS) lesions in the brain in the absence of ground truth, and to determine whether the two sequences, which differed only in echo time (TE), have the same accuracy. MATERIALS AND METHODS: We acquired FLAIR images at TE(1) = 90 ms and TE(2) = 155 ms from 46 patients with MS (24-69 years old, mean 45.8, 15 males) and 11 healthy volunteers (23-54 years old, mean 37.1, 6 males). Seven experienced neuroradiologists segmented lesions manually on randomly presented corresponding TE(1) and TE(2) images. For every image pair, a "surrogate ground truth" for each TE was generated by applying probability thresholds, ranging from 0.3 to 0.5, to the weighted average of experts' segmentations. Jackknife alternative free-response receiver operating characteristic analysis was used to compare experts' performance on TE(1) and TE(2) images, using successively the TE(1)- and TE(2)-based ground truths. RESULTS: Supratentorially, there were significant differences in relative accuracy between the two sequences, ranging from 8.4% to 12.1%. In addition, we found a higher ratio of false positives to true positives for the TE(2) sequence using the TE(2) ground truth, compared to the TE(1) equivalent. Infratentorially, differences in the relative accuracy did not reach statistical significance. CONCLUSION: The presented methodology may be useful in assessing the value of new clinical imaging protocols or techniques in the context of replacing existing ones, when the absolute ground truth is not available, and in determining changes in disease progression in follow-up studies. Our results suggest that the sequence with shorter TE should be preferred because it generates relatively fewer false positives. The finding is consistent with results of previous computer simulation studies.

Ruptured pseudoaneurysm of the internal maxillary artery complicating CT-guided fine-needle aspiration in an irradiated, surgical bed.

BACKGROUND: CT-guided fine-needle aspiration (FNA) is a safe procedure, but major complications can occur rarely. Pseudoaneurysm rupture in the head and neck region following CT-guided FNA is an emergency that can result in life-threatening hemorrhage. This case emphasizes the salient risk factors for pseudoaneurysm formation and rupture in the head and neck region following CT-guided FNA. METHODS: A patient was seen with oral and facial hemorrhage as a result of a ruptured pseudoaneurysm 11 weeks following CT-guided FNA in a previously irradiated surgical bed. RESULTS: The patient was treated with coil embolization in and around the pseudoaneurysm and discharged without any further complications. CONCLUSIONS: Although CT-guided FNA is a safe and effective procedure, some patients may be at increased risk for rare but major complications. Caution should be used in proceeding with CT-guided FNA in an irradiated surgical bed of the head and neck.

Recurrent late cerebral necrosis with aggressive characteristics after radiosurgical treatment of an arteriovenous malformation. Case report.

/Late cerebral radiation necrosis usually occurs within 3 years of stereotactic radiosurgery. The authors report on a case of recurrent radiation necrosis with rapid clinical deterioration and imaging findings resembling those of a malignant glioma. This 68-year-old man, who had a history of a left posterior temporal and thalamic arteriovenous malformation (AVM) treated with linear accelerator radiosurgery 13 years before presentation and complicated by radiation necrosis 11 years before presentation, exhibited new-onset mixed aphasia, right hemiparesis, and right hemineglect. Imaging studies demonstrated hemorrhage and an enlarging, heterogeneously enhancing mass in the region of the previously treated AVM. The patient was treated medically with corticosteroid agents, and stabilized temporarily. Unfortunately, his condition worsened precipitously soon thereafter, requiring the placement of a shunt for relief of obstructive hydrocephalus. Further surgical intervention was offered, but the patient's family opted for hospice care instead. The patient died 10 weeks after initially presenting to the authors' institution, and the results of an autopsy demonstrated radiation necrosis. Symptomatic radiation necrosis can occur more than a decade after stereotactic radiosurgery, necessitating patient follow up during a longer period of time than currently practiced. Furthermore, there is a need for more careful reporting on the natural history of such cases to clarify the pathogenesis of very late and recurrent radiation necrosis after radiosurgery and to define patient groups with a higher risk for these entities.

Imaging of spinal trauma.

Approximately 2% to 3% of blunt trauma victims suffer injury to the spinal column each year, often with devastating consequences. This article discusses clinical criteria for screening for spinal injury and the increasing roles of multidetector CT and MR imaging in the evaluation of spinal trauma. Both CT and MR imaging safety issues also are addressed. Lastly, the role of imaging in the evaluation of whiplash injury, instability, vascular injury, and delayed traumatic sequelae is discussed.

Complete regression of intracranial arteriovenous malformations.

BACKGROUND: Spontaneous and complete regression of intracranial arteriovenous malformations (AVMs) is a rare occurrence, with only 59 angiographically proven cases reported in the English literature. We present three new cases and perform a literature review to determine possible mechanisms underlying this unusual phenomenon. METHODS: Three patients with angiographically proven AVMs demonstrated complete obliteration of the AVM on follow-up angiography. Two patients had MRIs performed at the time of follow-up angiography. RESULTS: A literature review of all reported cases shows that the vast majority (88%) of spontaneously closing AVMs had a single draining vein as did our three cases. In addition, hemodynamic alterations of intracranial (IC) blood flow, including intracranial hemorrhage, were seen in a majority (79%) of patients, including two of our three cases. MRI was performed in two of our three cases and showed a thrombosed-draining vein in both. CONCLUSIONS: Complete spontaneous regression of intracranial AVMs is a rare occurrence. The phenomenon seems to require the interaction of hemodynamic changes in compromising or closing the limited, usually single, venous drainage pathway from the AVM. Hemorrhage may contribute to the effect by further compromising flow though the lesion, or it may merely be a phenomenon associated with the effects of venous hypertension on the AVM nidus.

Brain atrophy in mild or moderate traumatic brain injury: a longitudinal quantitative analysis.

BACKGROUND AND PURPOSE: Although mild or moderate traumatic brain injury (TBI) is known to cause persistent neurologic sequelae, the underlying structural changes remain elusive. Our purpose was to assess decreases in the volume of brain parenchyma (VBP) in patients with TBI and to determine if clinical parameters are predictors of the extent of atrophy. METHODS: We retrospectively assessed the total VBP in 14 patients with mild or moderate TBI at more than 3 months after injury and in seven patients at two time points more than 3 months apart. VBP was calculated from whole-brain MR images and then normalized by calculating the percent VBP (%VBP) to correct for intraindividual variations in cranial size. Clinical parameters at the time of trauma were evaluated for potential predictors of atrophy. Findings were compared with those of control subjects of similar ages. RESULTS: In the single time-point analysis, brain volumes, CSF volumes, and %VBP were not significantly different between patients and control subjects. In the longitudinal analysis, the rate of decline in %VBP (0.02 versus 0.0064 U/day, P =.05) and the change in %VBP between the first and second time points (-4.16 +/- 1.68 versus -1.49 +/- 1.7, P =.022 [mean +/-SD]) were significantly greater in patients. Change in %VBP was significantly greater in patients with loss of consciousness (LOC) than in those without LOC (P =.023). CONCLUSION: Whole-brain atrophy occurs after mild or moderate TBI and is evident at an average of 11 months after trauma. Injury that produces LOC leads to more atrophy. These findings may help elucidate an etiology for the persistent or new neurologic deficits that occur months after injury.

Alternative management considerations for ethmoidal dural arteriovenous fistulas.

BACKGROUND: Ethmoidal dural arteriovenous fistulas (EDAFs) are an unusual type of intracranial vascular lesion that commonly present with acute hemorrhage. They are often best treated surgically; however, recent endovascular advances raise questions concerning the best therapeutic approach. METHODS: We present 7 cases of EDAFs managed at this institution over a 6-year period, which demonstrate the broad spectrum of clinical behavior associated with the lesions. Four patients presented with intracranial hemorrhage, 1 patient with rapidly progressive dementia, 1 patient with a proptotic, red eye, and 1 with a retro-orbital headache. RESULTS: One patient underwent no treatment, 1 underwent embolization alone, 2 underwent embolization and resection, and 3 patients underwent resection alone. There was complete obliteration of the EDAF in all of the patients who underwent surgical resection. Embolization was performed through the external carotid circulation and not the ophthalmic artery. There were no treatment-related neurologic deficits. CONCLUSIONS: Treatment is best managed with a multidisciplinary approach, which emphasizes complete resection of the lesions with assistance from interventional neuroradiology techniques. However, each patient must be evaluated independently as treatment may vary depending on the angioarchitecture of the lesion.