Focal brain lactate accumulation in metformin-induced encephalopathy without systemic lactic acidosis: A case report suggesting mitochondrial vulnerability in lentiform fork sign

Metformin causes metabolic encephalopathy in some patients with end-stage chronic kidney disease, resulting in impaired consciousness and parkinsonism. This encephalopathy has a very characteristic magnetic resonance imaging feature in lentiform nuclei known as the “lentiform fork sign”. However, the mechanism is unknown. Here, we report a case of metformin-induced encephalopathy with a novel observation of lactate accumulation in the lentiform nuclei on magnetic resonance spectroscopy without systemic lactic acidosis. Since metformin is an inhibitor of mitochondrial complex-I, this focal brain lactate accumulation implies that a part of the pathogenesis of metformin-induced encephalopathy is the focal vulnerability of mitochondria to metformin in the lentiform nuclei. When metformin causes encephalopathy, not only testing for serum lactic acidosis and performing routine magnetic resonance imaging but also evaluation of brain lactate accumulation by magnetic resonance spectroscopy should be required to elucidate the etiology.