CNS Involvement by CLL Mimicking Demyelinating Disease: A Five-Year Case Study

Abstract Central nervous system involvement by chronic lymphocyte leukemia (CNS-CLL) without Richter transformation is a rare and hard-to-diagnose condition. Nonspecific symptoms and the need for a brain biopsy complicate diagnosis. We report a 58-year-old male with Rai stage 0 CLL who had severe neurological signs. His initial MRI suggested autoimmune-related demyelinating disease. However, high-dose steroids and intravenous immunoglobulin (IVIG) did not help. His neurological status continued to worsen. A multidisciplinary team used advanced imaging (PET-CT showing a hypermetabolic lesion with SUVmax 8.2) and stereotactic brain biopsy. Immunoglobulin heavy chain (IGH) gene clonal rearrangement showed identical clones (IGHV3-64*01/02/07) in both cerebral tissue and bone marrow. This confirmed CNS-CLL. Treatment with ibrutinib stabilized the disease and led to partial cognitive recovery. The patient survived five years without progression. This case and a literature review show that CNS-CLL can have atypical imaging and occur even in early-stage disease. Under targeted therapy, this rare condition may have a better prognosis than previously reported. The report highlights the importance of molecular studies for diagnosis and recommends a multidisciplinary diagnostic approach.