Mustafa, Rafid

Abstract BACKGROUND Dexamethasone is commonly used to manage peritumoral edema and alleviate neurologic symptoms in patients with intracranial tumors. The optimal dexamethasone dose for brain metastases is unknown and widely variable. Recent literature reports the most common regimen is 4 mg four times daily. However, the half-life of dexamethasone is 35-54 hours, suggesting that such frequent dosing may be unnecessary. We explored the dose-effect relationship of dexamethasone on brain metastases patient outcomes to improve quality of care. METHODS We retrospectively identified 100 patients (1/1/2016 – 12/31/2022) with brain metastases who were treated with dexamethasone and had adequate follow-up. All patients received standard oncologic care including chemotherapy, radiotherapy, and/or surgical intervention. We evaluated the association between dexamethasone dosing regimens (< 4 mg twice daily versus > 4 mg three times daily), clinical outcomes (performance status, clinical and radiographic response to corticosteroids, survival), and dexamethasone adverse effects during the acute presentation and at first neuro-oncologic follow-up. RESULTS Seventy-two patients received less frequent dexamethasone dosing (< 4 mg twice daily), while 28 received more frequent dexamethasone dosing (> 4 mg three times daily). Patients with higher frequency dexamethasone dosing were more likely to have radiographic evidence of midline shift (p < 0.001), compression of ventricles (p < 0.001), and herniation (p = 0.0020) at presentation. Those with more frequent dosing more often demonstrated radiographic response to dexamethasone (67.9% vs. 45.8%, p = 0.0323), but there were no differences in symptomatic improvement, Karnofsky Performance Status, seizure reduction, survival, or the frequency of adverse events (e.g., hyperglycemia, hypertension, infection, psychosis) between the two cohorts. CONCLUSIONS These results suggest that for most patients with brain metastases, less frequent dexamethasone dosing may lead to clinical outcomes that are similar to those patients who received more frequent dosing. However, higher doses of dexamethasone can be considered for those with more concerning radiologic features.

Abstract BACKGROUND Dexamethasone is commonly used for symptomatic management in primary central nervous lymphoma (PCNSL). The optimal dosing scheme for dexamethasone is unknown and practice patterns widely vary among clinicians. In this study, we explored the dose-effect relationship of dexamethasone on PCNSL outcomes to better influence quality care for these patients. METHODS We retrospectively identified 24 Mayo Clinic patients (1/1/2018 – 12/31/2022) with pathologically confirmed PCNSL who received dexamethasone. All patients otherwise received standard oncologic care including methotrexate-based systemic chemotherapy and/or radiotherapy. The association between dexamethasone dosing regimens and clinical outcomes (performance status, clinical and radiographic response, survival) in addition to potential adverse effects were evaluated in the acute phase of presentation and at first post-treatment oncology follow up. RESULTS Nine patients received less frequent dexamethasone dosing (4 mg twice daily or less), while 15 received more frequent dexamethasone dosing (4 mg four times daily). Fourteen patients received dexamethasone prior to biopsy, 2 of which (1 in each cohort) had a non-diagnostic biopsy and required a second procedure 3 weeks to 3 months later to confirm PCNSL diagnosis. There were no statistically significant differences in time to diagnosis from presentation or clinical and radiographic improvement including Karnofsky Performance Status, reduction in seizures, or survival between the two cohorts. Additionally, there were no differences in the frequency of adverse events (e.g., hyperglycemia, hypertension, infection, psychosis) between the two dosing regimens. CONCLUSIONS These results suggest that more frequent dexamethasone dosing is not associated with better clinical outcomes in the symptomatic management of PCNSL. Twice daily or less frequent dosing can be considered without compromising patient outcomes.

Abstract Pleomorphic xanthoastrocytomas (PXAs) are rare primary brain tumors that mainly affect children and young adults. We report a case of recurrent PXA in an adult and review the literature. To our knowledge, this is the first adult report highlighting clinical, CSF, and imaging findings of recurrent PXA with leptomeningeal spread. A 60-year-old woman presented with a 2-month history of fluctuating mental status, aphasia, low-back pain, progressive paraparesis, and urinary retention. She was previously diagnosed with a left temporal PXA 17 years prior and underwent gross total resection with no evidence of tumor recurrence for the next several years. Approximately 10 months prior to her current presentation, she was found to have radiographic recurrence of the left temporal PXA. She underwent gross total resection, with final pathology revealing anaplastic transformation, WHO grade 3, BRAF V600E mutation positive. She next underwent photon radiotherapy, and chemotherapy with temozolomide. She had good clinical and radiographic response to treatment for 8 months prior to developing her current symptomatology. MRI of the brain and spine showed local recurrence with new diffuse contrast enhancement of the spinal cord and nerve roots. Cerebrospinal fluid (CSF) analysis showed a total nucleated cell count of 10/mcL, protein >1250 mg/dL, glucose < 20 mg/dL, and xanthochromia. CSF cytology was positive for malignant cells consistent with PXA. Although PXA is often associated with a favorable prognosis, recurrence with anaplastic transformation can be associated with dissemination throughout the nervous system and worse outcomes. Despite the rarity of such cases, clinicians should remain vigilant, especially when anaplastic transformation occurs. Early detection of leptomeningeal involvement through thorough CSF analysis and appropriate imaging can facilitate prompt intervention and potentially improve patient outcomes.

Abstract Low-grade meningiomas with subtotal resection carry significantly shorter recurrence-free survival rates than those with gross total resection. We report the natural history of a case of low-grade meningioma after subtotal resection and review the literature. We aim to highlight known global health disparities in oncology treatment by describing a case of meningioma progression following subtotal resection. A 40-year-old Kenyan woman presented locally with headache, nausea, and vision loss over approximately a six month time period. A 5 cm olfactory groove meningioma was discovered, and she subsequently underwent subtotal resection that was likely limited due to hemorrhagic complications. Over the following two years, she developed progressive dizziness, nausea, gait instability, difficulty performing tasks, and visual loss prompting medical evaluation at our institution. Physical examination demonstrated blindness, bilateral proptosis with severe vertical gaze palsy, and prominent frontal bossing. MRI Brain revealed a 9 cm enhancing mass arising from the cribriform plate with elevation of an ununited overlying frontal craniotomy flap and apparent meningoceles extending through the presumed osteotomy bilaterally. She underwent successful resection with pathology demonstrating CNS WHO Grade 1 meningioma. Her postoperative neurologic exam showed subtle improvement, specifically in regards to orientation questions. In this patient, bone flap displacement from prior craniotomy allowed significant interval tumor growth while minimizing mass effect on brain parenchyma. This case highlights global health disparities in low-grade meningioma management related to appropriate healthcare access in underserved patients.

A 70-year-old male without prior psychiatric history presented with recurrent episodes (<60 seconds each, every 5-10 minutes) of left hemibody and right lower extremity jerking movements concerning for seizure with preserved awareness (Video). Examination showed left hemiparesis (leg > arm) in addition to right lower extremity weakness. Computed tomography showed a right parafalcine acute subdural hematoma (SDH). Clinical events did not recur after intravenous lorazepam (4 mg) and levetiracetam load (3500 mg), and his weakness improved. He was continued on levetiracetam and has since remained seizure free for 16 months. A 60-minute awake/sleep electroencephalogram (EEG) obtained 12 hours after administration of antiseizure medications showed low amplitude theta slowing (posterior predominant) in the range of 5-7 Hz. There was no apparent epileptiform activity or other abnormalities during the awake and sleep recording or photic stimulation. Focal seizures originate from pathologic disruption of neuronal activity within an isolated brain region, almost exclusively from a single hemisphere. Focal seizures may generalize bilaterally with associated impaired awareness. This is the first visual report demonstrating focal, bihemispheric clinical seizures, without generalization or impaired awareness. Rarely patients with generalized motor involvement from seizures have had retained consciousness and memory. The parafalcine SDH likely promoted epileptogenicity of the bilateral hemispheres. Acute and chronic SDH commonly present with seizures. Although there were no supportive electrographic findings, parasagittal epileptogenic lesions may be difficult for both clinical and electrographic localization. Post-event paresis with clinical improvement in the hours after event cessation supports clinical seizure.

We report a case highlighting key clinical, CSF, and imaging findings of recurrent pleomorphic xanthoastrocytoma with leptomeningeal spread.