Topography of hemispheric white matter pathology in ten cases of neuronal intermediate filament inclusion disease

Aims: To characterize the topography of white matter pathology in neuronal intermediate filament inclusion disease (NIFID), a rare subtype of frontotemporal lobar degeneration (FTLD) with “fused in sarcoma” (FUS)-immunoreactive inclusions. Material and methods: Fiber tracts from frontal and temporal lobes of 10 cases of NIFID. Method: Spatial patterns of the vacuolation, glial cell nuclei, and glial inclusions (GI) were studied across cortical fiber tracts from each case. Results: Vacuoles and glial cells in NIFID were distributed either in regularly-distributed clusters or in large diffuse clusters contrasting with typical control cases in which smaller clusters of glial cells were surrounded by more compact clusters of vacuoles. Axonal varicosities and GI were also observed in the precentral gyrus (PCG) of 4 NIFID cases. Depending on region, the densities of glial cells and vacuoles were either positively or negatively spatially correlated, but there were no spatial correlations between the densities of the GI and either the vacuoles or glial cells. Spatial patterns in white matter were similar to those reported in adjacent gray matter. Conclusion: 1) Pathological changes across the white matter in NIFID are topographically distributed, 2) there is a correlation between the development of vacuolation and gliosis, and 3) white matter and gray matter pathologies are closely related.