Altered sensorimotor cortex noradrenergic function in idiopathic REM sleep behaviour disorder – A PET study

IntroductionNoradrenergic denervation is thought to aggravate motor dysfunction in Parkinson's disease (PD). In a previous PET study with the norepinephrine transporter (NART) ligand ¹¹C-MeNER, we detected reduced NART binding in primary sensorimotor cortex (M1S1) of PD patients. Idiopathic rapid-eye-movement sleep behaviour disorder (iRBD) is a phenotype of prodromal PD. Using ¹¹C-MeNER PET, we investigated whether iRBD patients showed similar NART binding reductions in M1S1 cortex as PD patients. Additionally, we investigated whether ¹¹C-MeNER binding and loss of nigrostriatal dopamine storage capacity measured with ¹⁸F-DOPA PET were correlated.Methods17 iRBD patients, 16 PD patients with (PD^RBD+) and 14 without RBD (PD^RBD−), and 25 control subjects underwent ¹¹C-MeNER PET. iRBD patients also had ¹⁸F-DOPA PET. Volume-of-interest analyses and voxel-level statistical parametric mapping were performed.ResultsPartial-volume corrected ¹¹C-MeNER binding potential (BP^ND) values in M1S1 differed across the groups (P = 0.022) with the iRBD and PD^RBD+ groups showing significant reductions (controls vs. iRBD P = 0.007; control vs. PD^RBD+ P = 0.008). Voxel-wise comparisons confirmed reductions of M1S1 ¹¹C-MeNER binding in PD and iRBD patients. Significant correlation was seen between putaminal ¹⁸F-DOPA uptake and thalamic ¹¹C-MeNER binding in iRBD patients (r² = 0.343, P = 0.013).ConclusionsThis study found altered noradrenergic neurotransmission in the M1S1 cortex of iRBD patients. The observed reduction of M1S1 ¹¹C-MeNER binding in iRBD may represent noradrenergic terminal degeneration or physiological down-regulation of NARTs in this prodromal phenotype of PD. The correlation between thalamic ¹¹C-MeNER binding and putaminal ¹⁸F-DOPA binding suggests that these neurotransmitter systems degenerate in parallel in the iRBD phenotype of prodromal PD.     

Analysis of the diagnosis of Japanese patients with primary ciliary dyskinesia using a conditional reprogramming culture

BackgroundPrimary ciliary dyskinesia (PCD) is diagnosed through multiple methods, including transmission electron microscopy (TEM), a high-speed video microscopy analysis (HSVA), immunofluorescence (IF), and genetic testing. A primary cell culture has been recommended to avoid the misdiagnosis of secondary ciliary dyskinesia derived from infection or inflammation and improve diagnostic accuracy. However, primary cells fail to differentiate into ciliated cells through repeated passages. The conditional reprogramming culture (CRC) method, a combination of a Rho-kinase inhibitor and fibroblast feeder cells, has been applied to cystic fibrosis. The goal of this study was to evaluate the value of CRC in diagnosing PCD in Japanese patients.MethodsEleven patients clinically suspected of having PCD were included. Airway epithelial cells were obtained from an endobronchial forceps biopsy and cultured at the air-liquid interface (ALI) combined with CRC. Ciliary movement, ultrastructure, and mutated ciliary protein evaluation were performed using HSVA, TEM, and IF, respectively. Genetic testing was performed on some patients.ResultsCRC yielded dense and well-differentiated ciliated cells with a high success rate (～90%). In patients with PCD, the ciliary ultrastructure phenotype (outer dynein arm defects or normal ultrastructure) and IF findings (absence of the mutated ciliary protein) were confirmed after CRC. In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis.ConclusionsCRC could be a potential tool for improving diagnostic accuracy and contributing to future clinical and basic research in PCD.     

Utilidad diagnóstica de test cognitivos breves en el cribado de deterioro cognitivo

Introduction and objectivesThis study aims to assess and compare the diagnostic performance of brief cognitive tests for cognitive impairment (CI) screening recommended by the Spanish guidelines for the integral care of people with Alzheimer's disease and other dementias.Material and methodsWe performed a phase iii study into the accuracy of diagnostic tests, including patients with suspected CI in a primary care setting. All patients completed the Mini–Mental State Examination (MMSE), the Mini Examen Cognoscitivo (MEC), the Short Portable Mental Status Questionnaire (SPMSQ), the Memory Impairment Screen (MIS), the Clock Drawing Test (CDT), the Eurotest, the Fototest, and the Memory Alteration Test (M@T). CI was diagnosed independently by researchers blinded to scores on these tests. Diagnostic performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC).ResultsThe study included 141 individuals (86 with CI). The Eurotest and M@T (AUC ± SE: 0.91 ± 0.02 and 0.90 ± 0.02, respectively) took longer to administer (mean [SD]: 7.1 [1.8] and 6.8 [2.2] min, respectively) and have significantly better diagnostic performance compared to the MMSE, MEC, SPMSQ, and CDT, but not compared to MIS or Fototest (both with an AUC of 0.87 ± 0.03), with the latter taking less than half as long to administer (2.8 [0.8] min). The M@T and MIS only evaluate memory, and the latter cannot be administered to illiterate people.ConclusionThe most advisable tests for CI screening in primary care are the Eurotest, M@T, and Fototest, with the latter being the most efficient as it takes half as long to administer.     

单基因青光眼的临床实践指南

青光眼(glaucoma)是一组视网膜神经节细胞及其轴突变性的进行性视神经病,其典型临床特征为视乳头凹陷性萎缩和特征性视野缺损,遗传因素在其发病过程中起着重要作用。本指南主要介绍单基因变异相关的青光眼,包括原发性先天性青光眼(primary congenital glaucom a,PCG)和原发性开角型青光眼(primary open-angle glaucoma,POAG)的致病基因、疾病诊断以及临床咨询等方面,旨在规范单基因青光眼临床分子遗传诊疗,为临床医生对单基因青光眼诊治和遗传咨询服务提供参考。     

天灸罐联合少腹逐瘀汤治疗寒凝血瘀型原发性痛经临床观察

目的:观察天灸罐联合少腹逐瘀汤治疗寒凝血瘀型原发性痛经的临床疗效。方法:将90例寒凝血瘀型原发性痛经随机分为治疗组45例和对照组45例。对照组予少腹逐瘀汤治疗,治疗组在此基础上加用天灸罐治疗,均连续治疗5个月经周期。参照COX痛经症状量表(the Cox Menstrual Symptom Scale,CMSS)进行评价;测定两组治疗前后外周血中前列腺素F2a(Prostaglandin F2a,PGF2a)含量;比较两组痛经临床疗效。结果:总有效率组间比较,差异有统计学意义(P<0.05)。两组CMSS时间、程度及PGF2a含量治疗前后组内比较及治疗后组间比较,差异均具有统计学意义(P<0.05)。结论:天灸罐联合少腹逐瘀汤治疗寒凝血瘀型原发性痛经效果良好。