Case report of anorexia nervosa showing periventricular gliosis at autopsy

Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation and extreme weight loss. It has the highest mortality rate among all psychiatric disorders. Recent research indicates that malnutrition in AN patients induces various kinds of functional brain damage, but the pathophysiology of AN remains unclear. We report here the neuropathological findings of a 31-year-old Japanese woman. At age 24, she had a fear of gaining weight and reduced her dietary intake; she had extremely low body weight associated with overeating then self-induced vomiting. She was clinically diagnosed as having AN and was admitted to a psychiatric hospital with severe depression and suicidal thoughts. At age 31, she died despite intensive physical care and psychotherapy. Neuropathological examination revealed increased capillary blood vessels and slight fibrillary gliosis in the mammillary bodies, with similarities to Wernicke encephalopathy. The brainstem exhibited the characteristic features of central pontine myelinolysis, characterized by a sharply demarcated region of myelin pallor and relative sparing of axons. Senile changes, including neurofibrillary tangles/senile plaques, were not significant. Severe fibrillary gliosis was prominent around periventricular regions, including the caudate nucleus and nucleus accumbens, which are associated with cognition, emotion, and emotional behaviors via the dopaminergic pathways. These findings indicate that prolonged malnutrition in AN patients may induce brain damage, leading to dysfunction of the reward-related dopaminergic pathways. Furthermore, they represent the first pathological evidence that dysfunction of the cortico-limbic-striatal circuitry is involved in the pathophysiology of psychiatric symptoms in AN patients.