Chronic Lymphocytic Leukemia Infiltrating in the Brain

While earlier post-mortem studies show involvement of the central nervous system in 71% of patients with chronic lymphocytic leukemia (CLL), involvement intravitam is rare. A 72-year-old man with untreated, minimally symptomatic CLL developed subacute-onset encephalopathy and presented with severe hyponatremia and stress-induced cardiomyopathy. His initial head computed tomography scan was unremarkable. His mental status did not improve with careful sodium correction. Magnetic resonance imaging of the brain eventually revealed widespread T2 hyperintensities throughout the cerebral hemispheres, brainstem, and cerebellum. A cerebrospinal fluid analysis demonstrated elevated total nucleated cells (31/mcL, 89% lymphocytes), protein of 75 mg/dL, positive human herpesvirus 6 by polymerase chain reaction, and the presence of malignant CD5+ B cells, consistent with CLL. Brain biopsy confirmed direct infiltration of CLL cells in the brain parenchyma. He was started on zanubrutinib, which led to clinical and radiologic improvement. His neurologic recovery remained slow, and his family elected to transition to comfort-focused care. Our patient's case exemplifies a rare neurologic manifestation affecting <1% of patients with CLL. Despite partial clinical and radiologic response to zanubrutinib, he had a poor outcome, likely due to the extensive brain areas involved by CLL.