Case report of anorexia nervosa showing periventricular gliosis at autopsy

Abstract

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.

The Role of Glial Cells in Regulating Feeding Behavior: Potential Relevance to Anorexia Nervosa

“…Lately, serum GFAP and neurofilament light chain (NF-L) levels were increased in the patients compared to healthy controls and decreased upon short-term partial weight restoration, potentially indicating neural and glial damage during starvation [ 98 ]. Post-mortem analyses of patients with AN demonstrated reduced spine density as well as a changed spine morphology, which was paralleled by gliosis in periventricular brain regions and the ventromedial hypothalamus [ 99 , 100 , 101 ]. Furthermore, alterations in neuropil [ 102 ], synapses [ 103 ], and glial cells [ 36 ] have been reported in animal models of AN or starvation.…”

Neuropathological investigation of patients with prolonged anorexia nervosa

“…In animal studies of AN, some authors have reported reduced numbers of GFAP‐immunoreactive astroglial cells in the cortexes, and it has been proposed that starvation‐induced neuropsychological changes may occur in patients with AN 29,30 . However, all human postmortem studies of AN have found astrogliosis in the cortexes with neuronal degeneration 13,31 . We consider that these astroglial changes might correlate with the severity or duration of the illness, and might be associated with a deficit of the neuronal pathways.…”

“…29,30 However, all human postmortem studies of AN have found astrogliosis in the cortexes with neuronal degeneration. 13,31 We consider that these astroglial changes might correlate with the severity or duration of the illness, and might be associated with a deficit of the neuronal pathways. In other words, we suggest that these changes may be a pathophysiological feature of AN.…”

“…It is considered that ventricular enlargement stretches and compresses the periventricular regions, leading to interstitial edema or progressive axonal loss 36,37 . Both disorders also exhibit demyelination of the frontal lobes and arteriolar sclerosis of the periventricular white matter, 13,31 although the underlying mechanisms have not been clarified. Furthermore, the Wernicke encephalopathy‐like pathology of some of our cases, caused by vitamin B1 deficiency, has already been described in connection with AN 31,38 .…”

“…Furthermore, the Wernicke encephalopathy-like pathology of some of our cases, caused by vitamin B1 deficiency, has already been described in connection with AN. 31,38 The characteristic features of AN include gliosis, swelling of capillary endothelial cells, and capillary proliferation in the parenchymal regions. In addition, some cases showed central pontine myelinolysis, hypoxia caused by anemia, and hypoglycemia.…”