統合失調症の薬理学的治療中に発症した頸部のねじり性ジストニアと小脳運動失調を伴う著しい小脳萎縮を伴うジストニアを疑った1例

[A case suspected of dystonia with marked cerebellar atrophy with torsion dystonia of the neck and cerebellar ataxia that developed during pharmacologic schizophrenia treatment].

• Yumi Hoshino
• Masashi Yamazaki
• Yusuke Mochizuki
• Hideo Makishita
• Kunihiro Yoshida

抄録

46歳の統合失調症の男性は25歳から抗精神病薬を数種類服用していた。35歳頃から頸部の左ねじれ、後に失調性歩行に気付き、両症状は徐々に悪化していった。入院時、統合失調症のコントロールは良好であったため、オランザピン（5mg/日）と塩酸ビペリデン（1mg/日）を服用していた。両親は血縁関係になく，家族に精神神経疾患の既往歴はなかった。神経学的検査では，軽度の認知障害，水平眼振を伴う弛緩性眼球追従，軽度の構音障害，ジストニー性の姿勢と首の動き，両手の協調性の欠如，失調性の歩行を認めた．深部腱反射は膝蓋腱反射を除いて正常であったが，両側で亢進していた．病理的反射は陰性で，硬直，感覚障害，自律神経機能障害は認められなかった．眼科検査では両眼で黄斑外側黄体の菲薄化が認められ，黄斑変性症を示唆していた．入院後，すべての抗精神病薬を中止したが，ジストニアに変化はなかった．レボドパとトリヘキシフェニジル塩酸塩は効果がなかった．一般血液検査，尿検査，脳脊髄液検査では異常は認められなかった。脳MRIでは小脳萎縮と両側対称の視床病変を認めたが，脳幹萎縮や基底核の異常信号は認めなかった。I-IMP SPECTでも小脳の血流低下が認められた。希少疾病・未診断疾患イニシアチブが実施した全エクソームシークエンシングを含む遺伝学的スクリーニングでは，疾患の原因となる可能性のある変異は認められなかった．その結果，ジストニアが悪化し，右手と右足に雑用動作が出現した．顕著な小脳萎縮を伴うジストニア（DYTCA）を疑ったが，薬物誘発性ジストニアを除外できなかった．これまでに、黄斑ジストロフィーと脳MRI上の両側の視床病変はDYTCAでは報告されていなかった。これらの特徴がジストニアや小脳運動失調と主に関連しているかどうかは、現在のところ明らかにされていない。

A 46 year-old man with schizophrenia had taken several anti-psychotic drugs since 25 years of age. From ~35 years of age, he noticed occasional neck torsion to the left, and later an ataxic gait; both symptoms gradually worsened. On admission, the patient was taking olanzapine (5 mg/day) and biperiden hydrochloride (1 mg/day) because his schizophrenia was well controlled. His parents were not consanguineous, and there was no family history of neuropsychiatric diseases. On neurological examination, he showed mild cognitive impairment, saccadic eye pursuit with horizontal gaze nystagmus, mild dysarthria, dystonic posture and movement of the neck, incoordination of both hands, and an ataxic gait. Deep tendon reflexes were normal except for the patellar tendon reflex, which was exaggerated bilaterally. Pathological reflexes were negative and there was no sign of rigidity, sensory disturbance or autonomic dysfunction. Ophthalmological examinations detected thinning of the outer macula lutea in both eyes, indicative of macular dystrophy. After admission, all anti-psychotic drugs were ceased, but his dystonia was unchanged. Levodopa and trihexyphenidyl hydrochloride were not effective. General blood, urine and cerebrospinal fluid examinations showed no abnormalities. Brain MRI showed cerebellar atrophy and bilateral symmetrical thalamic lesions without brainstem atrophy or abnormal signals in the basal ganglia. I-IMP SPECT also revealed a decreased blood flow in the cerebellum. Genetic screening, including whole exome sequencing conducted by the Initiative on Rare and Undiagnosed Disease identified no possible disease-causing variants. The patient's dystonia worsened and choreic movements manifested on his right hand and foot. We suspected dystonia with marked cerebellar atrophy (DYTCA), but could not exclude drug-induced dystonia. Macular dystrophy and bilateral thalamic lesions on brain MRI have not been previously described in DYTCA. Whether these features might be primarily associated with dystonia or cerebellar ataxia now remains to be determined.