崎山 快夫

Sanayama H, Namekawa M, Sakiyama Y, et al. (March 22, 2024) Herpes Zoster Ophthalmicus Initially Diagnosed As Cluster Headache, Complicated by Delayed Eruption. Cureus 16(3): e56698. doi:10.7759/cureus.56698

BACKGROUND: Fabry disease (FD) is an inherited lysosomal storage disease caused by deficiency of α-galactosidase A (α-Gal A) encoded by the GLA gene. The symptoms of FD occur as a result of the accumulation of globotriaosylceramide (Gb3), comprising a substrate of α-Gal A, in the organs. Adeno-associated virus (AAV)-mediated gene therapy is a promising treatment for FD. METHODS: α-Gal A knockout (GLAko) mice were injected intravenously with AAV2 (1 × 1011 viral genomes [vg]) or AAV9 (1 × 1011 or 2 × 1012 vg) vectors carrying human GLA (AAV-hGLA), and plasma, brain, heart, liver and kidney were tested for α-Gal A activity. The vector genome copy numbers (VGCNs) and Gb3 content in each organ were also examined. RESULTS: The plasma α-Gal A enzymatic activity was three-fold higher in the AAV9 2 × 1012 vg group than wild-type (WT) controls, which was maintained for up to 8 weeks after injection. In the AAV9 2 × 1012 vg group, the level of α-Gal A expression was high in the heart and liver, intermediate in the kidney, and low in the brain. VGCNs in the all organs of the AAV9 2 × 1012 vg group significantly increased compared to the phosphate-buffered-saline (PBS) group. Although Gb3 in the heart, liver and kidney of the AAV9 2 × 1012 vg was reduced compared to PBS group and AAV2 group, and the amount of Gb3 in the brain was not reduced. CONCLUSIONS: Systemic injection of AAV9-hGLA resulted in α-Gal A expression and Gb3 reduction in the organs of GLAko mice. To expect a higher expression of α-Gal A in the brain, the injection dosage, administration route and the timing of injection should be reconsidered.

Early diagnosis and therapeutic intervention improve the quality of life and prognosis of patients with sarcopenia. The natural polyamines spermine and spermidine are involved in many physiological activities. Therefore, we investigated blood polyamine levels as a potential biomarker for sarcopenia. Subjects were Japanese patients >70 years of age who visited outpatient clinics or resided in nursing homes. Sarcopenia was determined based on muscle mass, muscle strength, and physical performance according to the criteria of the Asian Working Group for Sarcopenia (2019). The analysis included 182 patients (male: 38%, age: 83 [76-90] years). Spermidine levels were higher (p = 0.002) and the spermine/spermidine ratio was lower (p < 0.001) in the sarcopenia group than in the non-sarcopenia group. Polyamine concentration analysis showed that the odds ratios for age and spermidine changed in parallel with sarcopenia progression, and the odds ratio for the spermine/spermidine ratio changed inversely with the degree of sarcopenia progression. Additionally, when the odds ratio was analyzed with spermine/spermidine instead of polyamine concentrations, only for spermine/spermidine, the odds ratio values varied in parallel with the progression of sarcopenia. Based on the present data, we believe that the blood spermine/spermidine ratio may be a diagnostic indicator of risk for sarcopenia.

Several mechanisms strictly regulate polyamine concentration, and blood polyamines are excreted in urine. This indicates polyamine accumulation in renal dysfunction, and studies have shown increased blood polyamine concentrations in patients with renal failure. Hemodialysis (HD) may compensate for polyamine excretion; however, little is known about polyamine excretion. We measured whole-blood polyamine levels in patients on HD and examined the relationship between polyamine concentrations and indicators associated with health status. Study participants were 59 hemodialysis patients (median age: 70.0 years) at Minami-Uonuma City Hospital and 26 healthy volunteers (median age: 44.5 years). Whole-blood spermidine levels were higher and spermine/spermidine ratio (SPM/SPD) was lower in hemodialysis patients. Hemodialysis showed SPD efflux into the dialysate; however, blood polyamine levels were not altered by hemodialysis and appeared to be minimally excreted. The skeletal muscle mass index (SMI), which was positively correlated with hand grip strength and serum albumin level, was positively correlated with SPM/SPD. Given that sarcopenia and low serum albumin levels are reported risk factors for poor prognosis in HD patients, whole blood SPM/SPD in hemodialysis patients may be a new indicator of the prognosis and health status of HD patients.

症例は25歳女性で、発熱、頭痛、めまい、左半身のしびれをきたし、当院に救急搬送された。20歳時に両側感音難聴を発症し、他院で突発性難聴と診断された。その後、右補聴器を使用していたが、難聴が進行したため24歳時に人工内耳植込術を施行され、術後経過は良好であった。若年発症で血管支配域に一致しない頭部CT低吸収域があり、脳卒中様発作を考え、低身長、両側感音難聴があることを併せてMELASを疑い加療を開始した。エダラボンを開始したが意識レベルの低下をきたし、第5病日に経鼻胃管を挿入し、L-アルギニン、タウリン、ユビデカレノン、レボカルニチンの4剤の経管投与を開始した。第10病日に撮影した頭部CT検査で後頭葉への低吸収域の拡大を確認し、浮腫の軽減効果を期待してグリセリンを投与、左半側空間無視、着衣失行は残存するが自立歩行可能となり、第41病日に自宅退院した。

小児の神経系疾患に対する治療の向上や社会的支援体制の整備に伴い,多くの神経系疾患患者が成人を迎えることが可能となった.そのため,小児から成人期までの生涯医療が必要になった.2020年7月に日本神経学会小児-成人移行医療対策特別委員会が発足し,小児-成人移行医療の現状と課題を検討した.小児神経科医と脳神経内科医の双方がより良い小児-成人移行医療を構築するための問題意識を持っていた.しかし,医療体制には改善すべき課題があることが認識された.日本神経学会と日本小児神経学会が協力し,小児-成人移行医療への理解の促進や診療報酬上の評価に向けた働き掛けに取り組む.(著者抄録)

Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.

症例は49歳男性で、複視と右眼瞼下垂を自覚した。構音障害、下肢脱力、続いて嚥下障害が出現した。筋力低下は進行して歩行困難となり、緊急入院となった。重症筋無力症の悪化と考えピリドスチグミン、プレドニゾロン内服を開始した。筋力は改善傾向を呈し歩行も可能となったが、第7病日未明に脱衣し病棟を徘徊、聴取困難な1独語や意思疎通困難となる異常言動が出現した。次第に呼吸状態が悪化したため気管挿管しICU管理とした。重症筋無力症クリーゼとして単純血漿交換療法3日間、ステロイドパルス療法、ガンマグロブリン大量静注療法(IVIg)による治療を開始した。また発熱と発汗、流涎が顕著であったことから、セロトニン症候群が疑われ、並行してプロポフォールによる鎮静とシプロヘプタジン投与を開始した。複数の医療機関から多種・多剤の抗精神病薬を処方され薬物依存状態にあったことが判明した。治療継続により症状改善が得られ、第49病日に自宅退院とした。