Three presenile patients in which neuropsychological and neuroimaging examinations suggest possible progression to dementia with Lewy bodies

We report three presenile patients who were initially suspected of having Alzheimer's disease (AD) or being in the prodromal stage of AD, regardless of visuoperceptual dysfunctions in daily living, because they lacked the core features and prodromal non‐motor symptoms of dementia with Lewy bodies. Subsequently, progression to dementia with Lewy bodies was suspected based on neuropsychological and neuroimaging findings; additionally, one of the three patients suffered from visual hallucinations. Neuropsychological examinations such as subjective contours, cube copying and block design in the Wechsler Adult Intelligence Scale‐III revealed visuoperceptual dysfunction in all three patients even when other cognitive functions were rather preserved. Brain magnetic resonance imaging revealed no significant brain atrophy, including in the parieto‐occipital area and the hippocampus, while brain ¹⁸F‐fluorodeoxyglucose positron emission tomography demonstrated right dominant metabolic reductions in the occipital lobe, including the primary visual cortex, in all three patients. We suggest the possibility of progression to dementia with Lewy bodies, but not AD or posterior cortical atrophy. Regardless of the presence of core features and prodromal non‐motor symptoms, this progression is suggested when there are difficulties only in higher‐level visual processing such as subjective contours and block design in the Wechsler Adult Intelligence Scale‐III, no significant atrophy of the parieto‐occipital area and hippocampus on brain magnetic resonance imaging, and hypometabolism in the occipital lobe including the primary visual cortex on brain ¹⁸F‐fluorodeoxyglucose positron emission tomography.     

Myxoid glioneuronal tumor,PDGFRA p.K385‐mutant: clinical,radiologic, and histopathologic features

“Myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow‐up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports “myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.     

食管异物合并严重并发症的临床治疗分析

目的 探讨食管异物合并严重并发症的治疗方法。方法 回顾性分析解放军总医院第一医学中心耳鼻咽喉头颈外科2014年7月-2018年7月收治的23例合并食管穿孔、颈胸部感染等严重并发症的食管异物患者的临床资料,其中男11例、女12例,年龄2~87岁,病程2～11 d。术前CT扫描评估异物位置、食管损伤及周围炎症情况,其中异物位于第一狭窄16例、第二狭窄4例、第三狭窄1例及第四狭窄2例,合并食管穿孔23例、食管周围炎17例、食管周围脓肿3例、颈部脓肿2例、纵隔脓肿1例。23例中,行经硬性食管镜异物取出术17例、颈侧切开探查异物取出术5例、开胸探查异物取出术1例,围手术期配合胃肠减压、抗感染、营养支持等综合措施治疗。术后根据Stooler分级标准评价食管损伤后食管狭窄程度。结果 本组23例均顺利完成手术;经手术及围手术期综合治疗,均顺利拔除鼻饲管,行颈侧切开和开胸探查的患者均顺利拔除伤口引流管,均痊愈出院。1例患者于术后1个月并发颈段食管狭窄Ⅱ级,行食管扩张治疗后恢复正常。患者出院后随访3～5个月,23例均正常进食普通饮食,标准食管狭窄程度Stooler分级均为0级。结论 伴有严重并发症的食管异物应依据异物嵌顿部位及患者临床表现采取不同的手术方法取出异物,同时给予围手术期胃肠减压、抗感染、营养支持等综合治疗措施,多学科联合施救是挽救患者生命的重要举措。     

Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer's disease: association with cognitive impairment

The loss of zinc transporter 3 (ZnT3) has been implicated in age-related cognitive decline in mice, and the protein has been associated with plaques. We investigated the levels of ZnT3 and postsynaptic density protein 95 (PSD95), a marker of the postsynaptic terminal, in people with Parkinson's disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer's disease (AD, n = 16), and controls (n = 24), using semiquantitative western blotting and immunohistochemistry in 3 cortical regions. Standardized cognitive assessments during life and semiquantitative scoring of amyloid β (Aβ), tau, and α-synuclein at postmortem were used to investigate the relationship between ZnT3 and PSD95, cognition and pathology. Associations were observed between ZnT3 and PSD95 levels in prefrontal cortex and cognitive impairment (p = 0.001 and p = 0.002, respectively) and between ZnT3 levels in the parietal cortex and cognitive impairment (p = 0.036). Associations were also seen between ZnT3 levels in cingulate cortex and severity of Aβ (p = 0.003) and tau (p = 0.011) pathologies. DLB and PDD were characterized by significant reductions of PSD95 (p < 0.05) and ZnT3 (p < 0.001) in prefrontal cortex compared with controls and AD. PSD95 levels in the parietal cortex were found to be decreased in AD cases compared with controls (p = 0.02) and PDD (p = 0.005). This study has identified Zn²⁺ modulation as a possible novel target for the treatment of cognitive impairment in DLB and PDD and the potential for synaptic proteins to be used as a biomarker for the differentiation of DLB and PDD from AD.     

Neuroimaging in dementia

Over the last few years, advances in neuroimaging have generated biomarkers, which increase diagnostic certainty, provide valuable information about prognosis, and suggest a particular pathology underlying the clinical dementia syndrome. We aim to review the evidence for use of already established imaging modalities, along with selected techniques that have a great potential to guide clinical decisions in the future. We discuss structural, functional and molecular imaging, focusing on the most common dementias: Alzheimer's disease, fronto-temporal dementia, dementia with Lewy bodies and vascular dementia. Finally, we stress the importance of conducting research using representative cohorts and in a naturalistic set up, in order to build a strong evidence base for translating imaging methods for a National Health Service. If we assess a broad range of patients referred to memory clinic with a variety of imaging modalities, we will make a step towards accumulating robust evidence and ultimately closing the gap between the dramatic advances in neurosciences and meaningful clinical applications for the maximum benefit of our patients.     

颌下腺内鱼刺1例报告

<正>临床工作中颌下腺内异物相对少见,目前文献报道有笤帚梢杆经口底黏膜进入颌下腺内1例,采取手术治疗[1];吞咽麦芒1月后颌下不适,超声检查发现麦芒异物1例,手术取出异物[2];也有报道颌下腺内铅笔芯1例,但因病史较长文献未能提供异物移行颌下腺内的可能途径。本文报道咽部鱼刺异物移行颌下腺1例。1临床资料患者,男,42岁,因"右侧颌下区反复肿痛1月"入院。查体:右侧颌下区肿胀,肿胀区压痛明显,皮     

Ketogenic Effects of Multiple Doses of a Medium Chain Triglycerides Enriched Ketogenic Formula in Healthy Men under the Ketogenic Diet: A Randomized,Double-Blinded,Placebo-Controlled Study

Ketogenic diets, which are carbohydrate-restricted high-fat diets, may have therapeutic effects on various diseases, including cancer. However, ketogenic diets are often not standardized and, therefore, results are difficult to interpret. We previously investigated the usefulness of ketogenic diets in cancer therapy, where ketogenic formulas (KF) were used as supplements to enhance blood ketone bodies; however, the amount of KF was determined empirically with reference to blood ketone bodies levels. Here, to determine a standardized optimal amount of KF, we investigated temporal changes in blood ketone bodies (acetoacetic acid (AcAc), β-hydroxybutyrate (BHB)) and safety in 20 healthy individuals when KF was taken repeatedly under the conditions of a ketogenic diet (UMIN000034216). The diurnal variation in total ketone bodies, and AcAc and BHB levels significantly increased after lunch and after dinner, on the 4th day of KF administration. There were no significant safety issues related to KF in the context of anthropometric, metabolic, nutritional, urological and gastrointestinal parameters. In addition, ketogenic diets lead to changes in gut microbiota. KF showed a decrease in phylum Firmicutes. Our study provides baseline data of the usefulness of KF in a ketogenic diet.     

日本血吸虫重组线粒体相关蛋白免疫学活性鉴定

分子筛进一步纯化并复性的融合蛋白均能刺激家兔产生特异性抗体 ,粗提包涵体蛋白免疫家兔 ,血清抗体滴度为 1∶2 5 6 0 0 ,复性蛋白及经分子筛纯化的蛋白免疫的家兔血清抗体滴度均为 1∶5 12 0 0 ,Westernblot结果显示 ,粗提包涵体蛋白、复性蛋白及经过分子筛进一步纯化并复性的蛋白均能被重感染兔血清和rSj338/2 6GST特异性免疫兔血清所识别。攻击实验中 ,粗提包涵体蛋白和经分子筛纯化的蛋白分别可诱导小鼠产生 2 7.8% (P <0 .0 1)和 30 .4 % (P <0 .0 1)的减虫率 ,4 0 .4 % (P <0 .0 1)和 4 3.5 % (P <0 .0 1)肝总减卵率。粗提包涵体蛋白中rSj338和经分子筛纯化的蛋白中rSj338分别可诱导小鼠产生 13.9% (P <0 .0 5 )和 2 0 .0 % (P <0 .0 5 )的减虫率 ,30 .0 % (P <0 .0 1)和 4 1.7% (P <0 .0 1)肝总减卵率。结论　获得的日本血吸虫线粒体相关的重组融合蛋白(rSj338/2 6GST)具有良好的免疫学活性 ,重组融合蛋白 (rSj338/2 6GST)及rSj338均可诱导宿主抗血吸虫感染的部分保护力。