Department of Radiation Oncology, The Ohio State University, Columbus, Ohio, USA Department of Pediatric Neuro-Oncology, Nationwide Children’s Hospital, Columbus, Ohio, USA Department of Neurology, The Ohio State University, Columbus, Ohio, USA The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA Department of Pathology, The Ohio State University, Columbus, Ohio, USA Department of Neurosurgery, The Ohio State University, Columbus, Ohio, USA Department of Radiology, The Ohio State University, Columbus, Ohio, USA Department of Hematology, The Ohio State University, Columbus, Ohio, USA Department of Neurosurgery, Nationwide Children’s Hospital, Columbus, Ohio, USA Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA

no other distant metastases. She underwent video-assisted thoracoscopic surgery (VATS) biopsy of parietal pleural nodules, which confirmed metastatic renal cell carcinoma. Baseline contrast-enhanced MRI of brain was negative for intracranial metastases. She was started on first-line systemic therapy with pembrolizumab and axitinib. Restaging scans revealed good response with improvement in small pulmonary nodules with minimal residual pleural thickening in the right lung base. About 6 months after initial diagnosis, the patient presented with headaches and left-sided neck pain. A brain MRI with and without contrast revealed interval development of a 1.5 × 1.4-cm enhancing nodule in the left frontal lobe with mild to moderate surrounding vasogenic edema and mass effect. She also had an MRI of the cervical spine, which demonstrated multilevel degenerative changes but no metastatic disease. She was started on a short course of tapering Abstract Radiation necrosis (RN) is a concerning late toxicity after radiation therapy for brain metastases. The management of RN primarily depends on the extent of edema on imaging and presence of symptoms. Oral corticosteroids are the mainstay of management; however, they are not optimal for long-term management because of multiple side effects and drug interactions. Boswellia serrata is an extract derived from Indian frankincense, which is available as an over-the-counter supplement, and has been traditionally used in the treatment of asthma, arthritis and colitis due to its anti-inflammatory properties. Recent data have reported the benefits of Boswellia on reducing cerebral edema. We discuss a case report involving a patient with brain metastases treated with stereotactic radiosurgery who developed early RN and had a good response with resolution of postradiation edema with the use of Boswellia.

Background and purpose: Primary central nervous system lymphoma (PCNSL) lesions often show avid contrast enhancement on T1-weighted contrast-enhanced MRI sequences. However, several case reports and a clinical study have described PCNSL in patients with no contrast enhancement on MRI. We assessed whether overall survival (OS) time was related to any tumor characteristics (lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; and edema) on MRI in patients with PCNSL. Materials and Methods We retrospectively reviewed records (MRI features, pathology, and survival data) of all patients at our institution with PCNSL who had been seen from, 2007 through 2017, and had undergone pretreatment MRI. Results We identified 79 patients (42 men, 37 women) with a mean age at diagnosis of 61.7 ± 10.4 years. The mean OS duration was 44.6 ± 41.7 months. The most common pathological diagnosis (74 patients) was diffuse large B-cell lymphoma. No associations were found between OS time and lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; or edema. However, a sole patient with non-enhancing PCNSL on MRI was found to have low-grade disease, with prolonged survival (>83 months). Several other patients with leptomeningeal disease had a mean OS time of 80 months. Patients with hemorrhagic lesions had a mean OS of 25.5 months. Conclusions The survival time for patients with PCNSL may be longer than previously thought, especially for patients with leptomeningeal seeding and lesions with hemorrhagic components Also, non-enhancing tumors may be less aggressive than enhancing tumors.

Extent of resection of low grade glioma (LGG) is an important prognostic variable, and may influence decisions regarding adjuvant therapy in certain patient populations. Immediate postoperative magnetic resonance image (MRI) is the mainstay for assessing residual tumor. However, previous studies have suggested that early postoperative MRI fluid-attenuated inversion recovery (FLAIR) (within 48 h) may overestimate residual tumor volume in LGG. Intraoperative magnetic resonance imaging (iMRI) without subsequent resection may more accurately assess residual tumor. Consistency in MRI techniques and utilization of higher magnet strengths may further improve both comparisons between MRI studies performed at different time points as well as the specificity of MRI findings to identify residual tumor. To evaluate the utility of 3 T iMRI in the imaging of LGG, we volumetrically analyzed intraoperative, early, and late (~ 3 months after surgery) postoperative MRIs after resection of LGG. A total of 32 patients with LGG were assessed retrospectively. Residual tumor was defined as hyperintense T2 signal on FLAIR. Volumetric assessment was performed with intraoperative, early, and late postoperative FLAIR via TeraRecon iNtuition. Perilesional FLAIR parenchymal abnormality volumes were significantly different comparing intraoperative and early postoperative MRI (2.17 ± 0.45 cm3 vs. 5.47 ± 1.07 cm3, respectively (p = 0.0002)). A significant difference of perilesional FLAIR parenchymal abnormality volumes was also found comparing early and late postoperative MRI (5.47 ± 1.07 cm3 vs. 3.22 ± 0.64 cm3, respectively (p = 0.0001)). There was no significant difference between intraoperative and late postoperative Perilesional FLAIR parenchymal abnormality volumes. Intraoperative 3 T MRI without further resection appears to better reflect the volume of residual tumor in LGG compared with early postoperative 3 T MRI. Early postoperative MRI may overestimate residual tumor. As such, intraoperative MRI performed after completion of tumor resection may be more useful for making decisions regarding adjuvant therapy.

AbstractObjectivesTwo pilot studies of AR‐42, a pan‐histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra‐tumoral pharmacokinetics (PK) and pharmacodynamics (PD).MethodsPilot 1 is a subset analysis of a phase 1 study of AR‐42 in solid tumors, which included NF2 or sporadic meningiomas. Tumor volumes and treatment‐related adverse events (TRAEs) are reported (NCT01129193).Pilot 2 is a phase 0 surgical study of AR‐42 assessing intra‐tumoral PK and PD. AR‐42 was administered for 3 weeks pre‐operatively. Plasma and tumor drug concentrations and p‐AKT expression were measured (NCT02282917).ResultsPilot 1: Five patients with NF2 and two with sporadic meningiomas experienced a similar incidence of TRAEs to the overall phase I trial. The six evaluable patients had 15 tumors (8 VS, 7 meningiomas). On AR‐42, tumor volume increased in six, remained stable in eight, and decreased in one tumor. The annual percent growth rate decreased in eight, remained stable in three, and increased in four tumors. Pilot 2: Four patients with sporadic VS and one patient with meningioma experienced no grade 3/4 toxicities. Expression of p‐AKT decreased in three of four VS. All tumors had higher AR‐42 concentrations than plasma.ConclusionsAR‐42 is safe. Tumor volumes showed a mixed response, but most slowed growth. On a 40‐mg regimen, drug concentrated in tumors and growth pathways were suppressed in most tumors, suggesting this may be a well‐tolerated and effective dose. A phase 2 study of AR‐42 for NF2‐associated tumors appears warranted.Level of Evidence1b, 4.

Meningioangiomatosis is a rare benign lesion involving the central nervous system. Radiographic appearance can be highly variable which makes pre-operative diagnosis difficult. In this report, we describe meningioangiomatosis in a previously healthy 17-year-old woman who presented with seizures and continued headache and dizziness. This patient presented with a predominately calcified lesion on imaging and eventually underwent near total resection. Meningioangiomatosis is difficult to preoperatively identify, but is an important consideration as prognosis with surgical resection is typically good.

Abstract INTRODUCTION Treatment-induced cerebral necrosis (TN) is a challenging complication encountered in neuro-oncology. Diagnosis and treatment of TN remains poorly defined. METHODS In this single institution, retrospective study, consecutive patients with gliomas and TN between 01/01/2012 and 04/20/2020 at the OSUCCC were identified. Details of the tumor treatment, molecular markers, radiological and pathological findings of TN, as well as treatment, recurrence rate and management upon recurrence were collected. RESULTS Of the 53 patients analyzed, 37 had glioblastoma, 7 had anaplastic oligodendroglioma and 9 had grade II or III astrocytoma. MGMT promoter hypermethylation was present in 31/50 (59%) and IDH mutation in 17/53 (32%). Diagnosis of TN was based on histology in 43/53 (81%) or clinical/radiographic features in 10/53 (19%). Worsening of focal weakness (36%), seizures (9%) or being (30%) were common presentations at TN diagnosis. Patient with right compared to left hemisphere involvement were more symptomatic at TN diagnosis. (p=0.049). Bevacizumab (BEV) (51%), resection (28%), steroids only (9%) or Laser Interstitial Thermal Therapy (6%) were used to treat TN. Steroids were weaned off in 20/27 (74%) after receiving BEV. Among all treatments, BEV was significantly associated with a better outcome (resolution or partial improvement of enhancement in 84.6%) (p=0.0006, Bonferroni corrected p< 0.005). TN Recurrence occurred in 36%, 70% and 100% of the patients treated with BEV, resection and LITT respectively. The median duration to TN recurrence was 10 weeks (range: 3–70 weeks). Initial treatment used for TN, MGMT methylation and IDH mutation status did not predict TN recurrence. (p=0.074; p=0.819; p=0.607 respectively). CONCLUSIONS BEV appears to be a superior treatment to control TN overall. Recurrence of TN in patients previously treated with BEV was 36%. There was no difference in the risk of developing recurrent TN based on MGMT or IDH status.

Introduction: Conventional radiation therapy has been progressively replaced by fractionated stereotactic radiotherapy (FSRT) and single fraction radiosurgery for dealing with benign intracranial lesions. Purpose of our study is to investigate the safety and efficacy of FSRT in a series of patients with benign intracranial tumors. Methods: 31 patients with benign intracranial lesions treated with FSRT between 2006 and 2014 were retrospectively reviewed. Indications for treatment included post-operative residual tumor growth or symptomatic exacerbation in patients in whom surgery was not indicated. A clinical and radiological outcome evaluation was performed. Univariate analysis was executed to identify predictors for post-treatment neurological function and radiological tumor control. Results: Median age was 62 years (range 22-82). The lesions treated included 20 meningiomas, 2 vestibular schwannomas, 7 pituitary adenomas, 1 craniopharyngioma, 1 jugular-tympanic paraganglioma. Median clinical target volume was 14.59 cm(3) (range 0.43-159.06) and median planning treatment volume was 18.16 cm(3) (range 0.81-217.24). Median total dose was 45 Gy (range 25-54), and median daily fraction 4 Gy (range 1.8-9). At a median follow-up of 78 and 50 months, respectively clinical and neuroradiological, no tumor had larger dimensions, and only one lesion changed in a way other than size determining a concomitant clinical worsening. Other three patients deteriorated without evidence of radiological progression. Conversely, 12 patients improved clinically. No significant predictor for post-treatment neurological function or radiological tumor control was found. Conclusion: FSRT may represent, when indicated, a safe and effective treatment modality for benign intracranial tumors, especially for large/irregular lesions.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter degenerative disease characterized by both axonal and glial injury due to a defect in the CSF1R gene. In this report, we describe ALSP in a previously healthy 40-year-old woman presenting with insidiously progressive confusion, memory loss, and loss of social inhibitions. Characteristic magnetic resonance imaging findings for ALSP elucidated the diagnosis, including chronic foci of diffusion restriction in a non-vascular distribution, lack of temporal/infratentorial involvement, cortical sparing, and lack of enhancement. CSF1R genetic testing further confirmed the diagnosis and the patient underwent supportive medical management for symptom control. ALSP can pose a unique diagnostic challenge given its particular adult-onset presentation, but early recognition is key given the poor prognosis and the potential for family genetic testing.

BACKGROUND: Myelopathy of the dorsal columns is a rare complication of intrathecal (IT) chemotherapy that occurs most frequently with IT methotrexate and cytarabine. This diagnosis is made with a combination of magnetic resonance imaging, somatosensory evoked potentials, and elevated cerebrospinal fluid (CSF) protein levels, particularly myelin basic protein. CASE DESCRIPTION: A 73-year-old man with blastic plasmacytoid dendritic cell neoplasm and known central nervous system involvement underwent standard treatment, including 5 doses of IT cytosine arabinoside. Following this, he had documented CSF clearance of disease. One year later, he developed progressive lower extremity weakness, numbness, and bowel/bladder dysfunction. Magnetic resonance imaging and repeat CSF analysis demonstrated recurrence, and he underwent further IT administration of methotrexate and cytarabine. CSF clearance of malignant cells was again established. However, weakness progressed to quadriplegia; loss of bowel/bladder control; and severe sensory loss, particularly vibration and proprioception. Repeat magnetic resonance imaging demonstrated high signal intensity in bilateral posterior columns. A lower thoracic spine dorsal column biopsy revealed cord destruction and diffuse macrophage infiltration with profound destruction of the neuropil. CONCLUSIONS: Although dorsal column myelopathy has previously been described in association with IT chemotherapy, this has solely been diagnosed on the basis of clinical examination, electrodiagnostic criteria, radiographic findings, and CSF analysis. This case provides a pathologic evaluation of an antemortem obtained specimen revealing diffuse macrophage infiltration and profound destruction of the neuropil. Whereas the mechanism underlying spinal cord toxicity following IT chemotherapy remains largely unknown, this case demonstrates a potentially macrophage-mediated process.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare, reversible phenomenon that occurs several years after radiotherapy in patients treated for intracranial neoplastic lesions. Patients typically present with symptoms of headache, seizures, and other focal neurologic deficits concerning for stroke or disease recurrence. In this report, we describe SMART syndrome in a 70-year-old male who developed a persistent right temporal headache, right-sided neck pain, and new-onset seizures 12 years after surgical resection of a temporal anaplastic ependymoma followed by irradiation. We present this case to highlight typical disease presentation, imaging characteristics, and important differential radiologic considerations. Recognition of this delayed complication of brain tumor radiation is paramount given its self-limited course and favorable response to conservative therapy and to avoid misinterpreting imaging findings as tumor recurrence.

While magnetic resonance imaging (MRI) is superior to computed tomography (CT) in the evaluation of brain neoplasms, it remains important for physicians to be aware that CT, being the typical initial imaging modality for patients with neurologic complaints, can often delineate findings that suggest and potentially characterize a neoplastic process. In patients with oligodendroglioma, CT may allow physicians to suspect this specific neoplasm, even prior to obtaining an MRI examination. For example, striking calcifications within a suspected neoplastic lesion are a dominant feature of oligodendroglioma, more so than with other neoplastic lesions in the brain. This chapter reviews how CT can be a useful tool in patients with this type of brain tumor, whether the setting is CT imaging upon initial presentation, or in patients for whom MRI is contraindicated.

A 39-year-old previously healthy man presented with insidiously progressive paresthesia in his lower extremities and worsening of gait and balance. MRI demonstrated T2-hyperintense signal abnormalities involving the thalami, midbrain, dentate nuclei, and adjacent deep cerebellar white matter, which are characteristic of cerebrotendinous xanthomatosis (CTX) (figure). Magnetic resonance spectroscopy revealed typical lipid peaks at 0.9 and 1.3 ppm,(1) and serology analysis indicated sterol 27-hydroxylase deficiency,(2) confirming the diagnosis. CTX is a rare lipid storage disease with unique clinical and imaging findings, and effective treatment with positive outcomes if initiated early, raising the importance of awareness and early recognition of this disease.(2</SUP)

A 39-year-old previously healthy man presented with insidiously progressive paresthesia in his lower extremities and worsening of gait and balance. MRI demonstrated T2-hyperintense signal abnormalities involving the thalami, midbrain, dentate nuclei, and adjacent deep cerebellar white matter, which are characteristic of cerebrotendinous xanthomatosis (CTX) (figure). Magnetic resonance spectroscopy revealed typical lipid peaks at 0.9 and 1.3 ppm,1 and serology analysis indicated sterol 27-hydroxylase deficiency,2 confirming the diagnosis. CTX is a rare lipid storage disease with unique clinical and imaging findings, and effective treatment with positive outcomes if initiated early, raising the importance of awareness and early recognition of this disease.2

The list of differential considerations of lesions of the central skull base is long and includes many common tumors such as meningiomas and metastatic disease, which are discussed elsewhere in this book. In this chapter, we review the differential list of skull base tumors and discuss in more detail chordomas and to a lesser degree chondrosarcomas, two rare malignant lesions that classically involve the skull base. Although magnetic resonance imaging (MRI) has become the examination of choice in evaluation of intracranial tumors, in the skull base, computed tomography (CT) and MRI have complementary roles. CT is better at defining the complex bony anatomy and extent of bony involvement and MRI, because of its superior soft tissue contrast and multiplanar capability, is better at delineating the location, anatomic extension, and defining involvement of adjacent, critical neural, and vascular structures such as the cavernous sinus, optic chiasm, basilar artery and brain stem, for example. Although imaging studies cannot reliably distinguish chordoma from chondrosarcoma or other skull base lesions, defining the location and extent of the lesion are important factors in determining the optimal the surgical approach and in effective treatment planning. This is critical given that radical resection is the key factor in longer survival and improved quality of life.

Imaging has a critical role in the accurate diagnosis, grading, and monitoring of treatment response and complications of intracranial neoplasms. Distribution of growth, patterns of enhancement, and alteration of signal on magnetic resonance imaging or density characteristics on computed tomography can suggest a brain tumor. However, the differential diagnosis often includes entities that can simulate intracranial tumor, including inflammatory, infectious, demyelinating, and cerebrovascular diseases. This chapter aims to illustrate and differentiate brain neoplasm from other pathologic processes based on imaging characteristics and clinical parameters.