直井 為任

A 67-year-old man with hypertension and type 2 diabetes mellitus was admitted to our hospital because of left hearing loss and vertical diplopia. A neurological examination showed ocular torsion, skew deviation, and sensorineural hearing loss in the left ear. Brainstem and cerebellar neurological signs were not observed. Left middle cerebellar peduncle infarction was evident on magnetic resonance imaging. He was treated with anti-platelet, however, the infarct progressed after this administration. Ocular tilt reaction (OTR) involves the triad of ocular torsion, skew deviation, and head tilt. Ipsiversive OTR components associated with hearing loss can be early diagnostic signs of anterior inferior cerebellar artery infarction.

<p>症例は49 歳女性．段階的に進行する頭痛，意識障害，軽度の右麻痺，痙攣発作を呈し，左前頭葉に皮質下出血を伴う上矢状静脈洞血栓症と診断された．血液検査でプロテインS 活性の低下と，甲状腺機能亢進症が認められた．抗甲状腺薬と，ヘパリンによる抗凝固療法が行われたが，第5病日に両側性の小脳梗塞，第8 病日に右小脳出血を認め，第12 病日にリバーロキサバン10 mg の1日2 回投与に切り替えられた．その後は症状の悪化や頭蓋内出血の出現はなく，入院1 カ月後の画像検査では上矢状静脈洞の再開通を認め，後遺症なく，自宅退院した．脳静脈血栓症は頭蓋内出血を伴いやすく，ワルファリンより頭蓋内出血が少ないXa 阻害薬は有力な治療の選択肢になると考えられた．</p>

Scrub typhus is associated with various clinical symptoms. However, the pathogenesis of scrub typhus infection remains to be elucidated. A 73-year-old man was admitted to our hospital with consciousness disturbance and suspected meningoencephalitis. The patient's laboratory data showed deterioration and were indicative of hemophagocytic lymphohistiocytosis (HLH). A whole body examination to detect the trigger disease revealed an eschar, which is a characteristic of scrub typhus, on his back. His symptoms showed dramatic improvement after the administration of minocycline (MINO). This case report highlights that the clinical course of a case of scrub typhus meningoencephalitis that was cured with MINO.

Medullary hemorrhage is rare, and the causative role of hypertension still remains controversial. Cavernous angioma and other vascular malformations have been reported to cause medullary hemorrhage. A 53-year-old man was admitted to our hospital for vertigo. Medullary hemorrhage and multiple small hypointense lesions were detected on T2-star weighted magnetic resonance imaging (T2*W MRI). One and four months later, the appearance of new lesions confirmed the diagnosis of cerebral cavernous angioma. Cavernous angioma is often characterized by de novo appearance/progression on MRI. A follow-up MRI is required to diagnose cavernous angioma in patients with medullary hemorrhage.

Background Autosomal-recessive hereditary spastic paraplegias (AR-HSP) consist of a genetically diverse group of neurodegenerative diseases characterised by pyramidal tracts dysfunction. The causative genes for many types of AR-HSP remain elusive. We tried to identify the gene mutation for AR-HSP with cerebellar ataxia and neuropathy. Methods This study included two patients in a Japanese family with their parents who are first cousins. Neurological examination and gene analysis were conducted in the two patients and two normal family members. We undertook genome-wide linkage analysis employing single nucleotide polymorphism arrays using the two patients' DNAs and exome sequencing using one patient's sample. Results We detected a homozygous missense mutation (c.4189T&gt;G, p.F1397V) in the lysosomal trafficking regulator (LYST) gene, which is described as the causative gene for Chediak-Higashi syndrome (CHS). CHS is a rare autosomal-recessive syndrome characterised by hypopigmentation, severe immune deficiency, a bleeding tendency and progressive neurological dysfunction. This mutation was co-segregated with the disease in the family and was located at well-conserved amino acid. This LYST mutation was not found in 200 Japanese control DNAs. Microscopic observation of peripheral blood in the two patients disclosed large peroxidase-positive granules in both patients' granulocytes, although they had no symptoms of immune deficiency or bleeding tendency. Conclusions We diagnosed these patients as having adult CHS presenting spastic paraplegia with cerebellar ataxia and neuropathy. The clinical spectrum of CHS is broader than previously recognised. Adult CHS must be considered in the differential diagnosis of AR-HSP.

We present here a 25-year-old woman with genetically confirmed (p.R276L mutation in the GFAP gene) juvenile-onset AxD. Episodic vomiting appeared at age nine, causing anorexia and insufficient growth. Brain MRI at age 11 showed a small nodular lesion with contrast enhancement in the left dorsal portion of the cervicomedullary junction. Her episodic vomiting improved spontaneously at age 13, and she became neurologically asymptomatic. The enhancement of the lesion disappeared simultaneously, although the plaque remained. Longitudinal MRI observations, however, revealed insidiously progressive cervicomedullary atrophy without a signal change. This case broadens our knowledge of AxD: (1) molecular analysis of the GFAP gene is warranted in patients with MRI evidence of tumor-like lesions in the brainstem, particularly if they present with isolated episodic vomiting and/or anorexia; (2) the disease can be self-remitting for at least 12 years; (3) cervicomedullary atrophy, characteristic of the adult form, can be insidiously progressive without a signal change before the clinical symptoms appear.

Background Autosomal recessive hereditary spastic paraplegias (AR-HSP) constitute a heterogeneous group of neurodegenerative diseases involving pyramidal tracts dysfunction. The genes responsible for many types of AR-HSPs remain unknown. We attempted to identify the gene responsible for AR-HSP with optic atrophy and neuropathy. Methods The present study involved two patients in a consanguineous Japanese family. Neurologic examination and DNA analysis were performed for both patients, and a skin biopsy for one. We performed genome-wide linkage analysis involving single nucleotide polymorphism arrays, copy-number variation analysis, and exome sequencing. To clarify the mitochondrial functional alteration resulting from the identified mutation, we performed immunoblot analysis, mitochondrial protein synthesis assaying, blue native polyacrylamide gel electrophoresis (BN-PAGE) analysis, and respiratory enzyme activity assaying of cultured fibroblasts of the patient and a control. Results We identified a homozygous nonsense mutation (c.394C&gt;T, p.R132X) in C12orf65 in the two patients in this family. This C12orf65 mutation was not found in 74 Japanese AR-HSP index patients without any mutations in previously known HSP genes. This mutation resulted in marked reduction of mitochondrial protein synthesis, followed by functional and structural defects in respiratory complexes I and IV. Conclusions This novel nonsense mutation in C12orf65 could cause AR-HSP with optic atrophy and neuropathy, resulting in a premature stop codon. The truncated C12orf65 protein must lead to a defect in mitochondrial protein synthesis and a reduction in the respiratory complex enzyme activity. Thus, dysfunction of mitochondrial translation could be one of the pathogenic mechanisms underlying HSPs.