Clinical Summary

A 74-year-old man presented six months after right single lung transplant for idiopathic pulmonary fibrosis. He was on tacrolimus, mycophenolate mofetil, and prednisone. The illness began with three days of fever, myalgias, and malaise. He was febrile on admission but stable, and his neurological examination was normal.

He stayed febrile despite empiric antibiotics. Within days his mental status changed: he became confused, spoke little, followed commands inconsistently, and had episodes that looked like visual hallucinations. He was drowsy but rousable. With activation he developed rhythmic tremulous movements of the jaw, tongue, and upper limbs, and there were possible upper motor neuron signs at the right wrist. Power against gravity was preserved in all four limbs.

Initial non-contrast CT and a gadolinium-enhanced MRI on day 6 of illness were both normal. A week later, repeat CT showed new hypodensity in the inferior thalami, midbrain, and dorsal pons. Follow-up MRI then showed symmetric FLAIR hyperintensity in the caudate bodies, thalami, substantia nigra, pontine tegmentum, dentate nuclei, and central medulla, with diffusion restriction in the posterior limbs of the internal capsules and pachymeningeal enhancement. Serum and cerebrospinal fluid were sent.

Immunosuppression was reduced and intravenous immunoglobulin given. He did not recover, and died after withdrawal of life-sustaining therapy. Autopsy slides are available.

Discussion points

1. What is the differential diagnosis for this histologic pattern, and what is the most likely cause?
2. What serologic, molecular, and immunohistochemical testing would confirm the diagnosis, and what are the pitfalls?
3. How do the anatomic sites of injury explain the clinical findings, including the movement disorder and lower motor neuron involvement?