Epstein­Barr virus­associated primary central nervous system lymphoma in an immunosuppressed patient with a comorbid autoimmune disorder: A case report.

Patients with primary central nervous system lymphoma (PCNSL) typically present with non-focal neurological symptoms, including disorientation, poor balance and memory loss with unifocal or multifocal periventricular lesions seen on MRI. Deviations from these characteristic findings can delay diagnosis and lead to additional diagnostic tests being needed. The present study reports a 68-year-old man with a recent varicella zoster infection and history of acetylcholine receptor antibody-positive myasthenia gravis who received mycophenolate mofetil for 22 years. He presented with left eye vision changes and cognitive memory deficits. A brain MRI showed an enhancing lesion within his left medulla extending to the cerebellum. Cerebrospinal fluid analysis was positive for Epstein-Barr virus (EBV) and negative for malignancy. He was diagnosed with varicella zoster virus vasculopathy. At 3 months later, a repeat brain MRI showed multiple new enhancing lesions developing bilaterally along the periventricular white matter. Soon after, he presented to a local ER with acute left-sided blurry vision and worsening memory loss, and he began receiving steroids. Because of rapid symptom progression, he underwent resection of the left frontal lesion, which showed EBV-induced diffuse large B-cell lymphoma (DLBCL). Mycophenolate mofetil was discontinued, and within 24 h of one dose of intravenous 500 mg/m2 rituximab, he had a dramatic improvement in left eye vision and memory loss. He experienced mixed responses to rituximab after 3 cycles. Following one dose of high-dose methotrexate, he developed subsequent chronic kidney disease and required dialysis. He received whole-brain radiation therapy with craniospinal radiation and is currently in complete remission. An EBV-induced DLBCL diagnosis should be highly considered for patients with periventricular lesions and EBV-positive cerebrospinal fluid. Misdiagnosis or delay in PCNSL diagnosis because of atypical features in disease presentation and radiographic findings could lead to PCNSL progression and worsening neurological deficits.

Leukoencephalopathy During Daratumumab-Based Therapy: A Case Series of Two Patients with Multiple Myeloma.

Leukoencephalopathy in the setting of multiple myeloma (MM) is a rare demyelinating condition, with few reported cases in literature. Daratumumab is a CD38 targeted monoclonal antibody that has been widely used for the management of MM. In the absence of central nervous system (CNS) disease, many medication-induced leukoencephalopathy cases reported with MM, including daratumumab-induced, are associated with progressive multifocal leukoencephalopathy (PML) and John Cunningham (JC) virus. Currently, there are no reported cases of daratumumab-induced leukoencephalopathy among patients without CNS involvement or PML. We discuss 2 patients who developed leukoencephalopathy while receiving daratumumab-based therapy without evidence of PML or CNS disease. Both patients had baseline MRIs without significant white matter changes before daratumumab-based therapy. Patients began experiencing neurological deficits about 6 to 8 months after daratumumab-based therapy initiation. One patient passed away before being assessed for improvement of symptoms with daratumumab cessation. The second patient had some stabilization of symptoms after cessation; however, the leukoencephalopathy remained irreversible. As the class of anti-CD38 monoclonal antibodies expands in MM therapy, we highlight a potential treatment complication and the importance of detecting leukoencephalopathy early among patients receiving anti-CD38 therapy. We recommend vigilant monitoring of any new or worsening neurological symptoms to avoid serious complications of irreversible leukoencephalopathy.