Osmotic demyelination syndrome is a rare entity characterized by noninflammatory demyelination afflicting the central pons, basal ganglia, thalami, peripheral cortex, and hippocampi. Histopathologically, there is a destruction of myelin sheaths sparing the underlying neuronal axons due to the susceptibility of oligodendrocytes to rapid osmotic shifts often encountered in chronically debilitated patients. We present the temporal progression of signal abnormalities on sequential magnetic resonance imaging (MRI) scans in a middle-aged male initially presenting with altered mental status due to severe hyponatremia and subsequently developing rigidity, diagnosed as osmotic demyelination syndrome based on typical imaging findings and supportive laboratory parameters. This case demonstrates the importance of diffusion signal abnormalities as the first indicator of osmotic demyelination, evolution of extrapontine before pontine signal changes and the relative lack of correlation between patient's clinical profile and the extent of MRI signal abnormalities.

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