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。

Acute ischemic stroke (AIS) caused by major vessel occlusion has potentially poor outcomes. Early successful recanalization after symptom onset is an important factor for favorable outcomes of AIS. We present the case of a 74-year-old man with AIS who underwent the entire process from diagnosis to thrombolysis and endovascular treatment in a hybrid emergency room (ER) equipped with a multidetector computed tomography (CT) scanner and an angiography suite set-up. A hybrid ER can facilitate evaluation and definitive interventions in patients with AIS more quickly and safely and in one place, without the requirement for transfer to a CT scanner or angiography suite set-up. In the present case, the door-to-puncture time and door-to-reperfusion time were 85 and 159 min, respectively, which were shorter than those in the group conventionally treated for stroke in our institution. Further study is needed to confirm the effect of the hybrid ER system.

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。

59歳男。まぶしさや見え難さを自覚し、構音障害・ふらつきが加わり受診したが、頭部MRIに異常なく、陳旧性脳梗塞の影響と判断され、帰宅した。その後、車椅子移動となり、幻視や被害妄想が出現した。うつ病の診断で精神科に入院予定であったが、自力で動くことが困難となり、救急搬送された。入院時現症は、疎通性低下、体幹失調のため歩行困難であった。MRI拡散強調画像で大脳皮質の広範囲と両側尾状核・被殻に高信号を認め、脳波では周期性同期性放電、脳脊髄液14-3-3蛋白異常高値、プリオン蛋白遺伝子検査では遺伝子プリオンは否定的で、孤発性クロイツフェルト・ヤコブ病と診断した。経管栄養を導入し転院予定であったが、誤嚥性肺炎から非ケトン性高血糖性昏睡、多臓器不全を併発し、第43病日に死亡した。

Diagnosing clinical progressive supranuclear palsy (PSP) is challenging. We hypothesize that there are more cases of pathological PSP than have been clinically identified, but its diagnosis is challenging because the initial lesions and progression of PSP have not yet been clarified. The purpose of our study was to clarify the incidence of PSP in consecutive autopsy cases and identify pathological characteristics of early PSP. We investigated 324 consecutive autopsy patients from a general geriatric hospital (age, mean±SD=82.5±8.7 years). Paraffin sections of the midbrain were immunostained with anti 4-repeat tau antibodies (RD4). We selected cases showing RD4-positive neurofibrillary tangles and tufted astrocytes in the midbrain sections. Then, we used anti-phosphorylated tau antibody to immunostain sections from the basal ganglia, subthalamic nucleus, midbrain, pons, medulla, and cerebellum. Of the 324 patients, 35 had RD4-positive structures in the midbrain. From these 35 cases, we excluded those for which autopsies confirmed definite PSP (n=5) and cases of corticobasal degeneration (n=1), Alzheimer's disease (n=11), dementia of grain (n=10), and neurofibrillary tangles predominant forms of senile dementia (n=2), leaving 8 cases. We diagnosed these 8 cases as pure PSP-type tauopathy. Pure PSP-type tauopathy was detected in 2.5% of the consecutive autopsy cases, and this incidence was 1.6 times greater than that of neuropathologically definite PSP. This pure PSP-type tauopathy likely indicates preclinical stages of PSP. Furthermore, the novel neuropathological finding, which we term "preclinical PSP," is unique and has not previously been reported. In order to elucidate the causes and pathological mechanisms of PSP, preclinical PSP should be investigated further.

Diagnosing clinical progressive supranuclear palsy (PSP) is challenging. We hypothesize that there are more cases of pathological PSP than have been clinically identified, but its diagnosis is challenging because the initial lesions and progression of PSP have not yet been clarified. The purpose of our study was to clarify the incidence of PSP in consecutive autopsy cases and identify pathological characteristics of early PSP. We investigated 324 consecutive autopsy patients from a general geriatric hospital (age, mean±SD=82.5±8.7 years). Paraffin sections of the midbrain were immunostained with anti 4-repeat tau antibodies (RD4). We selected cases showing RD4-positive neurofibrillary tangles and tufted astrocytes in the midbrain sections. Then, we used anti-phosphorylated tau antibody to immunostain sections from the basal ganglia, subthalamic nucleus, midbrain, pons, medulla, and cerebellum. Of the 324 patients, 35 had RD4-positive structures in the midbrain. From these 35 cases, we excluded those for which autopsies confirmed definite PSP (n=5) and cases of corticobasal degeneration (n=1), Alzheimer's disease (n=11), dementia of grain (n=10), and neurofibrillary tangles predominant forms of senile dementia (n=2), leaving 8 cases. We diagnosed these 8 cases as pure PSP-type tauopathy. Pure PSP-type tauopathy was detected in 2.5% of the consecutive autopsy cases, and this incidence was 1.6 times greater than that of neuropathologically definite PSP. This pure PSP-type tauopathy likely indicates preclinical stages of PSP. Furthermore, the novel neuropathological finding, which we term "preclinical PSP," is unique and has not previously been reported. In order to elucidate the causes and pathological mechanisms of PSP, preclinical PSP should be investigated further.

Diagnosing clinical progressive supranuclear palsy (PSP) is challenging. We hypothesize that there are more cases of pathological PSP than have been clinically identified, but its diagnosis is challenging because the initial lesions and progression of PSP have not yet been clarified. The purpose of our study was to clarify the incidence of PSP in consecutive autopsy cases and identify pathological