Immunocytochemical and ultrastructural studies of Werdnig-Hoffmann disease

Neuronal alterations in two cases of Werdnig-Hoffmann disease (WH) were investigated immunocytochemically and ultrastructurally. Ballooned neurons (BNs) were found in anterior horn, Clarke's column, dorsal root ganglion and thalamus. Anti-phosphorylated neurofilament antibodies preferentially stained the peripheral perikarya and proximal neuronal processes of BNs, whereas anti-ubiquitin antibodies preferentially stained the central perikarya of BNs. Ultrastructurally, BNs showed degenerative changes ranging from a diffuse increase of neurofilaments to a centrally accentuated accumulation of mitochondria and vesicular or membranous profiles. Our studies suggest that ubiquitinated degradation products accumulate in the center of the BN's perikaryon and displace aberrantly phosphorylated neurofilaments to the periphery. BNs in WH probably reflect an intrinsic alteration in the metabolism of neurofilaments that is associated with regressive changes in the neuron and eventually neuronal death.