進行性多巣性白質脳症

Programmed cell death protein 1 (PD-1) is expressed by T cells during progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by the human-only JC polyomavirus (JCPyV). PD-1 checkpoint immunotherapy has benefited some PML patients, but reasons for its variable outcomes are unclear. Using mouse polyomavirus (MuPyV), we show that PD-1 loss acts in a brain-autonomous manner to increase the magnitude of brain-infiltrating CD4+ and CD8+ T cells and the function of virus-specific CD8+ T cells; in concert, brain virus levels decline and neuroinflammation increases. Deletion of PD-1 in CD4+ T cells, but not CD8+ T cells, recapitulates effects of global PD-1 loss. Single-cell RNA sequencing shows that PD-1-deficient CD8+ T cells cluster as effectors while transcripts associated with proliferation and function are upregulated with loss of PD-1. Thus, CD4+ T cell-intrinsic PD-1 signaling balances antiviral defense against neural injury during polyomavirus infection of the brain.

Diffuse gliomas with gliomatosis cerebri (GC) growth pattern are rare infiltrative tumors whose radiological presentation frequently mimics non-neoplastic white matter diseases. Strictly bilateral and symmetric involvement represents an exceptionally rare presentation, powerfully evoking leukodystrophy or metabolic leukoencephalopathy and constituting a major diagnostic pitfall. We report a 46-year-old woman with a 7-month history of progressive cognitive decline, dysarthria, and spastic paraparesis. CT demonstrated a hypodense corpus callosum lesion without enhancement. MRI revealed diffuse bilateral and remarkably symmetric T2/FLAIR white matter hyperintensities extending through the corpus callosum without gadolinium enhancement. Diffusion-weighted imaging showed focal restricted diffusion at lesion margins and within the splenium. MR spectroscopy demonstrated elevated choline (Cho/Cr ≈2), decreased N-acetylaspartate, prominent myo-inositol elevation, and a subtle creatine increase. Stereotactic biopsy confirmed high-grade diffuse glial proliferation with 5 mitoses per 10 high-power fields and IDH wild-type status. Unlike previously reported GC cases mimicking demyelinating disease with asymmetric multifocal involvement and low-grade histology, this case is distinguished by its strict bilateral symmetry and high-grade IDH wild-type biology. Symmetry does not exclude malignancy, and multimodal advanced MRI is essential to avoid diagnostic delay.

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