PMC3308920_01
Neuropathological features of concurrent MS and ALS. Left hemispheric leukocortical (within box) and periventricular lesions (arrow) (A). PLP staining of leukocortical plaque in A (inlay) demonstrating demyelination spanning grey and white matter (B), PG-M1 staining showing macrophage infiltration and microglia activation (C), and perivascular cuffing with cells resembling lymphocytes (D) within same lesion. Gross (E) and PLP-stained section (F) of pons (with cerebellum) demonstrating periventricular and parenchymal demyelination. PLP-stained section of demyelinated lesion in dorsal column of cervical spinal cord (arrow) (G) with diffuse microglia activation extending beyond lesional borders (PG-M1 staining) (H). Gross view of thinned and discolored ventral roots of lower cervical cord from case (I) compared to control (J). LBCV section of lumbar cord demonstrating significant loss of anterior horn cells in the case (K) compared to control (L). TDP-43 staining demonstrating intracytoplasmic neuronal inclusions in anterior horn cells in lumbar spinal cord (arrowheads) in case (M) compared to nuclear neuronal staining of the same area in a control (N).
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F1
Formalin-fixed paraffin-embedded sections of pre-frontal and sub-frontal cortex, hippocampus, cerebellum, pons, low and high cervical and thoracic, lumbar and sacral spinal cord were stained with Luxol Fast Blue and Cresyl Violet (LBCV), Palmgren silver, Proteolipid protein (PLP), CD68 (PG-M1), CD3, and TDP-43 antibodies (Figure 1). MS was supported by evidence of multiple discrete areas of inflammatory demyelination in prototypic locations, including cortex (subpial, leukocortical), periventricular region, corpus callosum (Figure 1A, B), pons (Figures 1E, F), cerebellar peduncle, and lateral and posterior columns of the spinal cord (Figure 1G). Microscopically, lesions were characterized by infiltration of macrophages in the epicenter of acute lesions and the border of chronic active lesions (Figure 1C); perivascular lymphocytic cuffing was noted in both (Figure 1D). Ventral nerve roots were discoloured and selectively thinned (Figure 1I), and a marked reduction (approximately 75%) of anterior horn cells at multiple serial lumbosacral cord levels when compared to controls was observed (Figure 1K, L). Microglial activation was noted in i) layer V of the motor cortex (where Betz cells were sighted), and ii) at various levels of the spinal cord (Figure 1H). ALS, and opposite to that found in MS (where small fibres are preferentially lost). Anterior horn cells in both cervical and lumbar cord demonstrated intracytoplasmic TDP-43 positive inclusions (Figure 1M), with no evidence of such inclusions in the cortical and deep gray matter regions examined.