Memory Lost

A 51-year-old man with acute myeloid leukemia presents on day 38 following allogeneic hematopoietic stem cell transplantation from a matched unrelated donor. He received myeloablative conditioning with busulfan and cyclophosphamide and has developed grade II chronic graft-versus-host disease affecting the skin and liver, managed with tacrolimus 2 mg twice daily and mycophenolate mofetil 1 g twice daily. Pretransplant serologies were notable for HSV IgG negative and VZV IgG negative; accordingly, acyclovir prophylaxis was not initiated. He is on fluconazole, trimethoprim-sulfamethoxazole, and letermovir for CMV prophylaxis (donor CMV seropositive, recipient seronegative).

Over the past five days his family has noted progressive confusion and short-term memory loss: he cannot recall conversations from an hour earlier, repeatedly asks the same questions, and has become increasingly disoriented to time. This morning he had a witnessed generalized tonic-clonic seizure lasting 90 seconds, which resolved spontaneously. He has had no fever, no headache, and no focal neurologic deficits. His wife notes he has seemed "not himself" for about a week.

On examination he is afebrile, blood pressure 128/74 mmHg, heart rate 88 bpm. He is alert but disoriented to date and place. He cannot recall three words after five minutes. There is no papilledema, no meningismus, and no focal motor or sensory deficits. Serum sodium is 126 mEq/L with urine osmolality 480 mOsm/kg and urine sodium 48 mEq/L, consistent with the syndrome of inappropriate antidiuretic hormone secretion. Serum CMV PCR is undetectable. EEG shows diffuse slowing with left temporal sharp waves.

MRI of the brain with and without gadolinium is performed.