Clinical Summary

An 80-year-old woman died after one year of progressive white matter degeneration and neurological decline characterized by mood disturbances, falls, and confusion.

The patient’s past medical history included breast ductal carcinoma in-situ (treated with mastectomy and radiotherapy), treated tuberculosis-associated uveitis, a prior vitreous biopsy with atypical lymphoid cells, type 2 diabetes mellitus, hypertension, dyslipidemia, hypothyroidism, permanent pacemaker placement, a stable pulmonary nodule, and chronic dyspnea of unclear etiology. 

Serial brain MRI demonstrated confluent supratentorial and infratentorial T2/FLAIR hyperintensity with patchy central restricted diffusion, without mass effect or enhancement; the lesions progressed over successive admissions. Infectious studies (including HSV, VZV, JC virus, mycobacteria, fungi, cryptococcal antigen, syphilis, and HIV) were negative, as were paraneoplastic and autoimmune panels (including AQP4, MOG, NMDA, and IgLON5), oligoclonal bands, and a whole-body FDG-PET. Her course was complicated by syndrome of inappropriate antidiuretic hormone secretion (SIADH) with persistent hyponatremia. A right frontal biopsy showed leukoencephalitis with perivascular lymphocytic cuffing, without demyelination, axonal loss, ischemia, necrosis, or vasculitis.

She was treated with high-dose intravenous corticosteroids, including pulse therapy, with transient improvement followed by continued deterioration. 

Discussion points

1. What is the differential diagnosis?
2. Further work-up?