Fig. 1

Neuropathologic findings. a, b The motor cortex shows neuronal loss and gliosis more prominently in a the lateral side than b the medial side. Some Betz cells are preserved only in the medial side of the motor cortex (arrowheads in b, c). c Macrophage accumulation in a Betz cell-sized hole (arrow in c), indicating ongoing neuronal degeneration, is evident in the medial side. d Myelin pallor in the bilateral lateral columns of the cervical and lumbar cord, and the left anterior column of the cervical cord, which indicate degeneration of the pyramidal tracts. Atrophy of the anterior horns is also evident in the cervical cord. e–h Severe neuronal loss and gliosis in e the cervical anterior horn, and f–h facial nucleus (arrows, atrophic neurons; arrowheads, reactive astrocytes; g and h, high magnification images of the square in f; h, GFAP-immunohistochemistry). i, j Bunina bodies in the remaining motor neurons of the facial nucleus (j, cystatin C-immunohistochemistry). k–s Phosphorylated TDP-43 (pTDP-43)-immunohistochemistry. Several pTDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs) and glial cytoplasmic inclusions (GCIs) in k the motor cortex, l hypoglossal nucleus and m subthalamic nucleus. n NCIs in the pontine nucleus. o Granulofilamentous and (left in p) filamentous NCIs and (right in p) GCI in the motor cortex. q GCIs in the white matter adjacent to the motor cortex. r Thick skein-like NCI in the hypoglossal nucleus. (s) Tube-shaped NCI in the anterior horn of the lumbar cord. Bar = 190 µm for a, b; 35 µm for c, g, h; 3 mm for d; 75 µm for e, f; 10 µm for i, j, o–r; 50 µm for k–n; 15 µm for s