統合失調症として長期入院していた特発性基底核石灰化症(Fahr病)の臨床病理学的特徴

Clinicopathologic Features of an Autopsied Patient with Idiopathic Basal Ganglia Calcification(Fahr's disease), Who Had Stayed in a Mental Hospital for a Longterm under the Diagnosis of Schizophrenia

抄録　特発性基底核石灰化症(Fahr病)は両側大脳基底核や小脳歯状核に石灰化を来す脳器質疾患で，無症状のものから多彩な精神神経症状を示すものまで様々である。最近，家族性例で遺伝子異常も見出されているが，発病メカニズムは不明である。筆者らは統合失調症として長期入院し，のちに認知障害，不随意運動などを呈し，遺伝子解析では既知の遺伝子変異は認められなかったものの，脳病理所見も勘案するとFahr病と考えられる症例を経験した。統合失調症の経過を辿り剖検されたFahr病例はまれなので報告する。不随意運動，認知障害を示す難治性の統合失調症で，頭部CT検査で脳の石灰化を認めた場合は，鑑別のためにCa代謝異常の有無を検査する必要がある。

　An 82-years-old woman died of respiraton pneumonia who had stayed in our mental hospital for a longterm under the diagnosis of schizophrenia.

　Her mental disorder presented with a sudden suicidal attempt at the age of nineteen years. Afterward, her grandiose erotomania and auditory hallucination were manifested. She was admitted recurrently to several mental hospitals and at the age of fifty nine years to our hospital. Her investigations in the form of hemogram, blood biochemistry including serum calcium and phosphorus levels, liver function tests, renal function tests, electroencephalogram, and electrocardiogram revealed no abnormality. Against intensive antipsychotics therapy her mental disorder was unchanged. At the age of sixty-seven years, cognitive dysfunctions(memory disturbance and disorientation to place)were occurred. A non-contrasted computalized tomography was performed, which showed the calcification of the bilateral globus pallidus, however, at this time the idiopathic basal ganglia calcification(IBGC)was not suspected but a physiological one. From her age of seventy two years, complex motor disturbances(oral dyskinesia, tremor of head and rigidity of extremities)followed each other.

　At autopsy, symmetric calcification in the globus pallidus, putamen, periaqueductal gray matter, and cerebellar dentate nucleus was evident. The calcification was observed in the tunica media of small artery, arterioles and capillaries. The autopsy pictures were consistent with those of IBGC. By whole-exome sequencing genomic DNA extracted from the patient's fresh-frozen brain, we identified no mutation in SLC20A2, PDGFRB, PDGFB or XPR1. From the clinicopathologic features this case was definitely diagnosed as a sporadic IBGC.

　This case teaches us to the importance of comprehensive medical assessment including brain computed tomography for psychiatric patients with a cognitive dysfunction and extrapyramidal symptoms.