Genomic characterization of an esthesioneuroblastoma with spinal metastases: illustrative case.

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare neoplasm of the sinonasal tract. Currently, the optimal treatment includes maximal resection combined with radiotherapy and/or chemotherapy. Although ENBs often recur and have an aggressive clinical course, spinal metastases are extremely rare and the underlying molecular mechanisms are poorly understood. OBSERVATIONS: Here, the authors describe a 50-year-old male with an aggressive ENB, initially treated with resection and chemotherapy/radiation, who developed multiple thoracic and lumbar spinal metastases. The authors performed targeted exome sequencing on both the resected primary tumor and biopsied spinal metastases, which revealed 12 total variants of unknown clinical significance in genes associated with the PI3K/AKT/mTOR pathway, chromatin remodeling, DNA repair, and cell proliferation. Six of these variants were restricted to the metastatic lesion and included missense mutations with predicted functional effects in GRM3, DNMT3B, PLCG2, and SPEN. LESSONS: This report discusses the potential impact of these variants on tumor progression and metastasis, as well as the implications for identifying potential new biomarkers and therapies.

Optic Perineuritis in an Asymptomatic SARS-CoV-2 Infection.

INTRODUCTION: Optic perineuritis (OPN) is a previously undescribed sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here we present a case of OPN that developed several weeks after initial confirmation of the presence of novel coronavirus RNA in the nasopharynx by polymerase chain reaction assay and subsequent confirmation of SARS-CoV-2 IgG seropositivity in the absence of other systemic inflammatory or infectious markers. CASE REPORT: An asymptomatic 71-year-old man with noninsulin-dependent diabetes mellitus (NIDDM) tested RNA positive for SARS-CoV-2 during a routine screening of patients at a skilled nursing facility. ~3 weeks after the positive SARS-CoV-2 polymerase chain reaction test, the patient developed subacute ophthalmoparesis of the left eye, horizontal diplopia, retro-orbital pain, and frontal headache. An urgent magnetic resonance imaging of the head and orbits suggested OPN. Cerebrospinal fluid studies were without evidence of other infectious, inflammatory, neoplastic, or paraneoplastic processes. He was started on a 5-day course of high-dose intravenous steroids and later transitioned to oral steroid therapy. Sixteen days after the initiation of steroid therapy, the patient had no headache or retro-orbital pain and demonstrated a marked improvement in horizontal gaze. CONCLUSION: SARS-CoV-2-associated neurological sequelae have been increasingly recognized during the current coronavirus disease 2019 pandemic. The present case suggests that patients with confirmed SARS-CoV-2 positivity, even without pulmonary or other classic manifestations of active infection, may manifest diverse clinical presentations including postinfectious OPN that could be related to an underlying autoimmune reactive inflammatory response.

Intracranial bleeding following soccer-related head trauma in a young student with occult factor VII deficiency.

It is important to obtain coagulation tests to assess bleeding risk in trauma patients undergoing emergency surgery when a bleeding disorder may be obscured. Identifying specific clotting factor defects is critical in successful patient management.

Role of FDG-PET/MRI, FDG-PET/CT, and Dynamic Susceptibility Contrast Perfusion MRI in Differentiating Radiation Necrosis from Tumor Recurrence in Glioblastomas.

BACKGROUND AND PURPOSE: To compare the utility of quantitative PET/MRI, dynamic susceptibility contrast (DSC) perfusion MRI (pMRI), and PET/CT in differentiating radiation necrosis (RN) from tumor recurrence (TR) in patients with treated glioblastoma multiforme (GBM). METHODS: The study included 24 patients with GBM treated with surgery, radiotherapy, and temozolomide who presented with progression on imaging follow-up. All patients underwent PET/MRI and pMRI during a single examination. Additionally, 19 of 24 patients underwent PET/CT on the same day. Diagnosis was established by pathology in 17 of 24 and by clinical/radiologic consensus in 7 of 24. For the quantitative PET/MRI and PET/CT analysis, a region of interest (ROI) was drawn around each lesion and within the contralateral white matter. Lesion to contralateral white matter ratios for relative maximum, mean, and median were calculated. For pMRI, lesion ROI was drawn on the cerebral blood volume (CBV) maps and histogram metrics were calculated. Diagnostic performance for each metric was assessed using receiver operating characteristic curve analysis and area under curve (AUC) was calculated. RESULTS: In 24 patients, 28 lesions were identified. For PET/MRI, relative mean ≥ 1.31 resulted in AUC of .94 with both sensitivity and negative predictive values (NPVs) of 100%. For pMRI, CBV max ≥3.32 yielded an AUC of .94 with both sensitivity and NPV measuring 100%. The joint model utilizing r-mean (PET/MRI) and CBV mode (pMRI) resulted in AUC of 1.0. CONCLUSION: Our study demonstrates that quantitative PET/MRI parameters in combination with DSC pMRI provide the best diagnostic utility in distinguishing RN from TR in treated GBMs.

Differentiation of recurrent spinal ependymoma from postradiation treatment necrosis through multiparametric PET-MR and perfusion MRI.

A 67-year-old male presented with papilledema and back pain localized to the T10 level. Initial workup revealed multifocal spinal ependymoma which was resected and treated with external beam radiotherapy. Nine years after treatment, the patient had a relapse of back pain, and MRI was inconclusive in distinguishing posttreatment radiation necrosis from recurrent tumor. We present the first described report with the utilization of multiparametric positron emission tomography-magnetic resonance imaging and perfusion MRI to distinguish recurrent spinal ependymoma from radiation necrosis.

Rectal carcinoid tumor metastasis to a skull base meningioma.

Carcinoid tumors are rare, slow-growing neuroendocrine tumors that most frequently develop in the gastrointestinal tract or lungs and have high potential for metastasis. Metastasis to the brain is rare, but to another intracranial tumor is extremely rare. Of the intracranial tumors, meningiomas are the most common to host metastases, which may be related to its rich vascularity and E-cadherin expression. We describe the case of a 65-year-old female with active chemotherapy-treated neuroendocrine carcinoma who presented with left-sided facial numbness, headaches, and blurry vision. Initial imaging revealed a 1 cm irregular dural-based left petrous apex mass suggestive of a meningioma that was re-imaged four months later as a rapidly enlarging, extra-axial, mass extending into the cavernous sinus, effacing Meckel's cave that resembled a trigeminal schwannoma. Pathology revealed a carcinoid tumor metastatic to meningioma. While the mass displayed characteristic imaging findings of a schwannoma, rapid growth in the setting of known active malignancy should prompt the clinician to consider mixed pathology from metastatic disease or a more aggressive meningioma.

Histologically Proven Radiation-Induced Brainstem Glioma 93 Months After External Beam Radiotherapy for Pituitary Macroadenoma: Radiation Treatment Dose and Volume Correlation.

Patient is a 29-year-old with a history of recurrent growth hormone-secreting pituitary macroadenoma diagnosed 12 years prior to presentation. Eight years prior to current presentation, the patient underwent re-resection and received 50.4 Gy external beam radiotherapy (EBRT) in 28 fractions of 1.8 Gy each. Serial postradiation MRIs demonstrated regression in pituitary tumor size. Patient presented with new headaches 7.5 years after completing EBRT. Brain MRI demonstrated new FLAIR hyperintensity and contrast enhancement within the pons and medulla, corresponding to the 36 Gy isodose line of each radiation dose fraction. Differential diagnosis included radiation necrosis and radiation-induced glioma (RIG). The patient's neurologic exam worsened over the following 4 months. MRI showed progressive increase in mass effect, extent of FLAIR hyperintensity, and contrast enhancement in the brainstem. Stereotactic-assisted biopsy showed infiltrating astrocytoma with moderate atypia. A PubMed search showed this is the first case of histologically verified brainstem RIG correlated with 3-dimensional conformational radiation therapy dose and volume planning following EBRT for a pituitary adenoma. The rare occurrence of brainstem RIG after radiation therapy for pituitary tumor supports the need for long-term imaging monitoring of such patients.

Impact of inflammation on brain volume in multiple sclerosis.

OBJECTIVE: To study changes in brain volume measured monthly in patients treated for relapsing multiple sclerosis due to loss of tissue and the appearance of inflammation. DESIGN AND PATIENTS: The results from T2/fluid-attenuated inversion recovery axial images from 13 consecutive monthly 3-T brain magnetic resonance imaging tests conducted on 74 patients diagnosed with relapsing multiple sclerosis in the BECOME study were used to calculate whole brain volumes using automated software analysis tools. The patients had been randomized to receive treatment with interferon beta-1b or glatiramer acetate. Ongoing inflammation was studied by counting the number of combined active lesions and measuring the volume of gadolinium enhancement. A mixed-effects model was used to analyze brain volumes over time. RESULTS: There was a significant decrease in brain volume over time but there was no difference in its rate of change by age, sex, frequency of ongoing inflammation, multiple sclerosis type, or randomized treatment assignment. The mean rate of brain volume change per month from multivariable models was -1.1 cm(3) (95% CI, -1.5 to -0.6) and during times of magnetic resonance imaging activity, it increased transiently by an average of 1.2 cm(3)/lesion (95% CI, 0.7 to 1.7) and 7.1 cm(3)/1 cm(3 )of gadolinium volume. In a model with both measures, combined active lesions were independent predictors of brain volume but gadolinium volume was not. CONCLUSION: Two major changes in brain volume occur in patients with relapsing multiple sclerosis, a steady decrease likely due to tissue loss with overlapping transient increases due to the appearance of inflammation.

Clinical consequences of MRI activity in treated multiple sclerosis.

BACKGROUND: Inflammation on brain MRI is the most sensitive marker of disease activity in multiple sclerosis (MS) but its clinical consequences remain controversial. OBJECTIVE: Here we investigated the clinical consequences of MRI activity in MS subjects treated with two different first line disease modifying agents. METHODS: Seventy-five treatment-naïve subjects with relapsing-remitting MS (N = 61) or clinically isolated syndromes at risk of MS (N = 14) from the BECOME study that had been randomized to interferon beta-1b (N = 39) or glatiramer acetate (N = 36) and followed for up to two years by monthly brain MRI optimized to detect inflammatory activity were studied for the clinical consequences of lack of MRI remission. RESULTS: MRI remission occurred in 46.4% of participants transiently and in 23.2% completely while it was never achieved in 30.4%. There was no difference by treatment in MRI remission, progression of physical disability, or cognitive function. The percentage of relapse-free subjects was 87.5% for the group in complete MRI remission, 47.6% in the group never in remission and 59.4% in the group in transient remission (p = 0.017). Similar differences were observed for six-month-confirmed worsening of ambulatory function as measured by the timed 25 foot walk (p = 0.026) and by Expanded Disability Status Scale (EDSS) (p = 0.10). Cognitive function was lowest at baseline for the group that never reached MRI remission on treatment; this group improved the least upon repeated cognitive testing during the two years of treatment (p < 0.001). CONCLUSIONS: Lack of MRI remission during treatment with interferon beta-1b or glatiramer acetate is associated with higher relapse rate and worsening of physical and cognitive function.

Serum levels of CXCL13 are elevated in active multiple sclerosis.

There is increasing recognition of the important role that B cells play in the pathogenesis of multiple sclerosis (MS). Recently it was reported that the B cell chemokine CXCL13 is elevated in MS serum and cerebrospinal fluid. Here we study whether serum levels of CXCL13 are associated with active MS. We measured serum levels of CXCL13 by enzyme-linked immunosorbent assay in 74 patients with relapsing MS randomized to interferon beta 1b or glatiramer acetate and examined with monthly 3 T brain MRI scans optimized for detection of gadolinium-enhancement for up to 2 years. The median (range) serum levels of CXCL13 pre-treatment were 40 (3-171) pg/ml. Serum levels of CXCL13 were significantly higher at times of active brain MRI scans (p < 0.01). Furthermore, serum levels were higher in patients who never reached MRI remission compared with those in complete (p < 0.01) or partial (p = 0.01) remission. There was a significant positive correlation between the pattern of serum levels of CXCL13 and MRI activity during the first (r = 0.33, p < 0.05) and the full 2 years (r = 0.35, p < 0.01) of the study. Treatment with interferon beta 1b or glatiramer acetate did not affect serum CXCL13. We conclude that the serum levels of the B cell chemokine CXCL13 are associated with active MS.