Mitochondrial alterations in pellagra-associated central chromatolysis: Comparison with ballooned achromatic neurons of other etiologies

Neuronal central chromatolysis (CC) is the histopathological hallmark of pellagra encephalopathy, a neurological deficit resulting from vitamin deficiencies. Pellagrous CC neurons are morphologically similar to ballooned achromatic neurons in other conditions but the distinct pathomechanisms remain unclear. We performed a clinico-neuropathological analysis of 10 autopsy cases of pellagra encephalopathy. The pellagra encephalopathy cases were immunohistochemically compared with disease controls, including cases of axonal injury and neurodegenerative diseases. Electron microscopic evaluation and immunohistochemical examinations targeting mitochondrial fragmentation were performed for a representative case. Four of 10 pellagra encephalopathy patients exhibited prolonged impairment of consciousness distinguishable from alcohol withdrawal delirium. Pellagrous CC neurons were negative for cytoskeletal markers whereas ballooned achromatic neurons in the disease control cases were positive. Immunohistochemical analysis of mitochondrial markers revealed that CC neurons exhibited more intense immunoreactivity for COX-IV and mitochondrial fissure factor compared to the disease controls. Transmission electron microscopy of these CC neurons revealed a marked increase in the mitochondria with amorphous densities. These findings indicate that the pathomechanism of pellagrous CC is distinct from that of the ballooned achromatic neurons of other etiologies. Mitochondrial alterations in pellagrous CC neurons suggest that neuronal energy deficits resulting from nicotinamide adenine dinucleotide deficiency induce mitochondrial fragmentation.