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We report the sixth autopsy case of a patient with aceruloplasminemia. He was the younger brother of the first reported autopsy case of this disease. Among autopsy cases with aceruloplasminemia reported to date, he had the longest duration of neurologic disorders. The neuropathologic findings showed that the basal ganglia and dentate nuclei were most severely affected. The most striking finding in the present case was that marked iron deposition was evident in the cerebral cortex. Many enlarged or deformed astrocytes and globular structures, both of which were heavily iron loaded, were found in the cerebral cortex as well as in the basal ganglia. Pyramidal neurons in his cerebral cortex were fewer in number than observed in the previous reported cases. There was a negative correlation between the number of cortical pyramidal neurons and globular structures. The present case clearly indicates that the neuropathologic process in aceruloplasminemia extends beyond the basal ganglia to the cerebral cortex with time., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Hashimoto's encephalopathy (HE) is thought to be caused by disorders of immune mechanisms. Although immunologically mediated central nervous system vasculitis or unidentified anti-neuronal autoantibodies have been suspected of causing HE, its pathogenesis is still unclear. For the study presented here, two patients with typical clinical and laboratory/electrophysiological findings of HE were analyzed to clarify the role of anti-neuronal autoantibodies in the pathogenesis of HE. The autopsied brain of one of the patients was histopathologically examined. For Western blotting analysis and immunohistochemistry, serum and purified immunoglobulin G obtained from the other patient were used. Autopsy revealed no evidence of central nervous system vasculitis or other abnormal findings in the brain. The patient's serum contained an anti-neuronal autoantibody that immunohistochemically labeled neurons of mouse and human cerebral cortices and reacted with the 36-kDa antigenic protein present in a soluble fraction obtained from human cerebral cortex. Our results indicate that anti-neuronal autoantibodies may be associated with the pathogenesis of HE.

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin (Cp) gene. The neuropathological hallmark of this disease is intracellular iron overload, which is thought to lead to neuronal cell death through increased oxidative stress. We evaluated and characterized protein oxidation in the brain of a patient with this disease. The protein carbonyl content in the cerebral cortex of the patient was elevated compared to controls. Furthermore, peptide mass fingerprinting and partial amino acid sequencing identified glial fibrillary acidic protein (GFAP) as the major carbonylated protein in the cerebral cortex of the patient. In conjunction with the facts that Cp mainly localizes to astrocytes in the central nervous system and that astrocytes are loaded with much more iron than neurons in the cerebral cortex, our findings indicate that Cp deficiency may primarily damage astrocytes. We speculate that the dysfunction of astrocytes may be causatively related to neuronal cell loss in aceruloplasminemia.

The article focuses on a medical report which discusses hypothalamic involvement in nonparaneoplastic, nonherpetic limbic encephalitis. Hypothermia is a life-threatening state that can be caused by several different mechanisms, such as extended exposure to a cold environment, drug overdose, sepsis, and endocrine disturbance. Here, the article report a nonherpetic nonparaneoplastic limbic encephalitis patient with a severe episodic hypothermia attack. Episodic hypothermia in this patient was thought to be due to the direct association of the central thermoregulatory center by encephalitis.