The diagnostic utility of cerebrospinal fluid alpha-synuclein analysis in dementia with Lewy bodies – A systematic review and meta-analysis

BackgroundDementia with Lewy Bodies (DLB) can be difficult to distinguish clinically from other dementias.ObjectiveTo investigate the diagnostic utility of CSF alpha-synuclein in differentiating between DLB and other dementias.MethodsElectronic databases were systematically searched for studies investigating reproducible alpha synuclein quantification methods. Random effects model was used to calculate weighted mean difference (WMD) and 95% confidence intervals between DLB and other groups.ResultsA total of 13 studies, comprising 2728 patients were included. Mean CSF alpha-synuclein concentration was significantly lower in DLB patients compared to those with Alzheimers disease (AD) [WMD ?0.24; 95% CI, ?0.45, ?0.03; p = 0.02]. No significant difference was found between patients with DLB compared to Parkinsons disease [WMD 0.05; 95% CI, ?0.17, 0.28; p = 0.65] or other neurodegenerative conditions.ConclusionCSF alpha synuclein may be of diagnostic use in differentiating between DLB and AD. We propose several recommendations to guide better design of future studies.     

“Cannonballs” and psammoma bodies: Unusual cytologic features of metastatic pulmonary small‐cell carcinoma in a pleural effusion

Large three‐dimensional cell aggregates and psammoma bodies are usually encountered in benign serous effusions (mesothelial hyperplasia and endosalpingiosis), mesotheliomas, and metastatic papillary carcinomas. We report a case of pulmonary small‐cell carcinoma occurring in an 88‐year‐old woman that initially presented with a malignant pleural effusion characterized cytologically by a predominance of large three‐dimensional neoplastic cell aggregates (“cannonballs”), associated with rare psammoma bodies. Although the crowded three‐dimensional tumor‐cell aggregates did not allow detailed cytologic examination, the diagnosis of metastatic small‐cell carcinoma could be established noting the characteristic chromatin features of the occasional single neoplastic cells and the characteristic “cell‐in‐cell” and “stack‐of‐coins” arrangements of rare small clusters of neoplastic cells. Immunoperoxidase stains showing positivity of the tumor cells for CD56, synaptophysin, and TTF1 further supported this diagnosis. Endobronchial ultrasound‐guided fine‐needle aspiration of a mediastinal lymph node subsequently confirmed the diagnosis of pulmonary small‐cell carcinoma. Metastatic pulmonary small‐cell carcinoma should be considered in the differential diagnosis of serous effusions showing large three‐dimensional neoplastic cell aggregates and psammoma bodies to prevent a potential diagnostic pitfall. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

锥形束CT诊断颌面部异物1例

<正>张口受限为颌面外科的常见疾患,但颌面部异物引起张口受限多为个案报道[1-3]。准确定位异物位置及其形状大小,是外科手术取出异物,保证手术成功的关键。锥形束CT(cone beam computed tomography,CBCT)因其独特的三维成像特点,可以精确定位,更好地引导外科手术的顺利进行[4-6]。现对我院收治的1例颌面部异物引起的张口受限患者的临床资料进行报道,并结合文献回顾对CBCT在颌面异物诊断中的应用价值进行讨论。     

食管嵌顿性异物内镜治疗分析

目的 评价内镜治疗嵌顿性食管异物的有效性和安全性.方法 回顾性总结78例嵌顿性食管异物患者的病例资料,收集食管异物的种类、数量、嵌顿部位、滞留时间,相关食管病变,内镜治疗方法、治疗时间以及并发症发生情况,并对影响并发症发生及治疗时间相关因素进行统计分析.结果食管上段最易发生嵌顿(80.8％,63/78)和穿孔(66.7％,8/12);11例异物滞留时间超过24 h,其余67例不足24 h;所有患者经内镜成功取出异物(只有2例穿孔患者取出异物后转耳鼻喉科或胸外科接受进一步治疗),治疗过程中无一例死亡,主要并发症为出血(13例,16.7％),其次为黏膜撕裂伤(7例,9.0％)和穿孔(1例,1.3％),总的并发症发生率为26.9％(21/78);异物形状、滞留时间及是否穿孔是影响内镜治疗时间和并发症发生率的主要因素(P＜0.05).结论 内镜治疗嵌顿性食管异物是安全和有效的方法.已造成食管穿孔的异物,滞留时间不超过24h且CT提示食管管腔外无脓肿形成者,可首选内镜治疗.     

Endoscopic Management for Delayed Diagnosis of a Foreign Body Penetrating the Esophagus into the Lung

A 31-year-old male presented with chest pain started after eating chicken about 2 weeks earlier. Upper endoscopy and Computed tomography scan of the chest revealed a sharp chicken bone penetrating the esophageal wall into the right lung. The foreign body was removed endoscopically using a rat-tooth forceps, followed by prophylactic placement of a metal stent across the esophageal perforation site. Foreign body-induced perforation is one of the common etiologies of benign esophageal perforations. Although the primary treatment is surgery, endoscopic therapy may be appropriate in individualized cases like our patient.     

28例路易体痴呆患者的视频-多导睡眠图分析

目的研究路易体痴呆（DLB）患者的视频～多导睡眠图,探讨路易体痴呆患者的睡眠结构。方法对临床诊断DLB28例及正常对照28人进行研究。所有入组者均进行简易精神状态检查量表（MMSE）和视频～多导睡眠图（Video-PSG）监测。结果（1）睡眠结构分析：与对照组相比,DLB组总睡眠间期时间（SPT）减少,差异具有统计学意义（P〈0．05）;总睡眠时间（TST）减少、睡眠效率（SE）下降、总醒觉时间（TWT）、入睡后清醒时间（WASO）增多、1期睡眠时间（TS1）、2期睡眠时间（TS2）、NREM睡眠时间（TNREMS）和REM睡眠时间（TREMS）均明显减少,差异具有统计学意义（P〈0．01）;（2）睡眠呼吸事件分析：DLB组与对照组相比,各项指标差异均无统计学意义（P〉0．05）;（3）其他睡眠事件分析：与对照组相比,DLB组睡眠期周期性肢体运动次数（PLMS）、快动眼睡眠行为异常（RBD）明显增多,差异具有统计学意义（P〈0．01）。结论DLB患者存在睡眠结构紊乱,睡眠异常行为亦很常见。视频-多导睡眠图对于研究DLB患者的睡眠障碍很有帮助。     

Focus on germ-layer markers: A human stem cell-based model for in vitro teratogenicity testing

Human induced pluripotent stem cells (hiPSC) were used to develop an assay format that may deliver information on teratogenicity of drugs. A human pluripotent stem cell scorecard panel was used to monitor the expression of 96 marker genes that are indicative of the stem cell state or differentiation into the ectoderm, mesoderm and endoderm lineages. We selected a human episomal iPS cell line for the assay based on karyotype stability, initial pluripotency, differentiation capacity and overall gene expression variability. The assay is based on embryoid body formation and was developed to be simply automated. In this proof of concept study, we used eight reference compounds (valproic acid, all-trans-retinoic acid, thalidomide, methotrexate, hydroxyurea, ascorbic acid, penicillin G and ibuprofen) to test the technical performance of the assay (readout stability) in concentration-response and time-course experiments. We also found that each compound affected marker gene expression in a different way. Various forms of data analysis identified 19 out of 96 early developmental genes as potential predictive markers for teratogenicity. Machine-learning models were run to exemplify how the assay will be developed further. The preliminary results from these analyses suggest that the assay could be suitable for the pre-screening of candidate pharmaceutical compounds. The approach presented here points a way towards development of a human cell-based assay that could replace the murine EST currently used to screen for early indications of potential teratogenicity of drug candidates.     

Infectious Agents as Potential Drivers of α-Synucleinopathies

α-synucleinopathies, encompassing Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are devastating neurodegenerative diseases for which available therapeutic options are scarce, mostly because of our limited understanding of their pathophysiology. Although these pathologies are attributed to an intracellular accumulation of the α-synuclein protein in the nervous system with subsequent neuronal loss, the trigger(s) of this accumulation is/are not clearly identified. Among the existing hypotheses, interest in the hypothesis advocating the involvement of infectious agents in the onset of these diseases is renewed. In this article, we aimed to review the ongoing relevant factors favoring and opposing this hypothesis, focusing on (1) the potential antimicrobial role of α-synuclein, (2) potential entry points of pathogens in regard to early symptoms of diverse α-synucleinopathies, (3) pre-existing literature reviews assessing potential associations between infectious agents and Parkinson's disease, (4) original studies assessing these associations for dementia with Lewy bodies and multiple system atrophy (identified through a systematic literature review), and finally (5) potential susceptibility factors modulating the effects of infectious agents on the nervous system. © 2022 International Parkinson and Movement Disorder Society