Clinical markers of early nigrostriatal neurodegeneration in idiopathic rapid eye movement sleep behavior disorder

Background

Rapid eye movement sleep behavior disorder (RBD) is an early feature in α synucleinopathies and may precede other clinical manifestations of disease for several years. Olfactory dysfunction and mild motor abnormalities (MMAs) are highly prevalent in prodromal α synucleinopathies such as RBD and are suspected to be predictive neurodegenerative markers. Because both markers also are highly prevalent in the healthy elderly population, the discriminative value to detect an early neurodegenerative process is unclear.

Methods

We examined 28 patients with idiopathic RBD (iRBD) without manifest neurodegenerative disease to determine diagnostic accuracy of MMAs and olfactory dysfunction in identifying patients with early nigrostriatal degeneration in transcranial sonography (TCS) and ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single-photon emission computed tomography (¹²³I-FP-CIT-SPECT).

Results

Sixty-three percent of our participants showed MMAs which were strongly associated with abnormal TCS and ¹²³I-FP-CIT-SPECT findings. The discriminative value in detecting participants with early nigrostriatal degeneration was excellent (area under the receiver operating characteristic [ROC] curve, 0.84 [P ? .003] for TCS and 0.79 [P ? .066] for ¹²³I-FP-CIT-SPECT). Olfactory dysfunction was present in 78% of iRBD participants, but it was not linked with neuroimaging abnormalities or MMAs. Olfactory dysfunction did not discriminate participants with early nigrostriatal degeneration (area under the ROC curve, 0.54 [P ? .747] for TCS and 0.31 [P ? .225] for ¹²³I-FP-CIT-SPECT). Early RBD manifestation but no demographic (e.g., age, gender) or clinical characteristics of RBD (e.g., duration, severity of RBD) were associated with neuroimaging abnormalities in TCS and ¹²³I-FP-CIT-SPECT.

Conclusions

Unlike olfactory dysfunction, MMAs discriminate patients with early nigrostriatal degeneration in iRBD. Early RBD manifestation seems to be an additional risk factor which aggravates neurodegenerative risk.     

Availability of the serotonin transporter in patients with alcohol dependence

Abstract

Objectives. Evidence has suggested that the serotonin transporter (SERT) plays a role in the pathogenesis of alcohol dependence, anxiety and depression and that polymorphisms of the serotonin-transporter-linked promoter region (5-HTTLPR) may influence the SERT. This study evaluated the differences in SERT availability between healthy controls and alcoholic patients and the impact of 5-HTTLPR polymorphisms on SERT availability. Methods. Eleven healthy controls and 28 alcoholic patients were recruited. SERT availability was measured in vivo with single photon emission computed tomography and ¹²³I-labelled 2-((2-((dimethyl-amino)methyl)phenyl)thio)-5-iodophenylamine in the midbrain, thalamus and striatum. Each subject was genotyped for the 5-HTTLPR polymorphism. Results. Compared to healthy controls, there was a significantly lower availability of SERT in the midbrain among patients with pure alcohol dependence (pure ALC). Of patients with anxiety, depression and alcohol dependence (ANX/DEPALC), the carriers of one L_A allele showed a significantly higher availability of SERT in the striatum compared to non-L_A carriers. After Bonferroni correction, these significances vanished. There were no significant differences in SERT availability between controls and ANX/DEP ALC. Conclusions. The results suggest that pure alcoholics may have lower SERT availability in the midbrain; the 5HTTLPR polymorphism may influence SERT availability in ANX/DEP ALC. These findings may serve as a springboard for future large-scale studies.     

Ketogenic diet therapy is effective in encephalitis with refractory seizures

Abstract

Objective and importance:

Although ketogenic diet therapy is effective in refractory seizures in childhood, its effect on adult encephalitis with similar refractory seizures and prolonged encephalopathy has not been well reported.

Clinical presentation:

We report here a case of a 22-year-old man with acute encephalitis with refractory repetitive partial seizures (AERRPS).

Intervention:

Partial seizures of the face developed to repeated generalized convulsions, which were refractory against anti-epileptic drugs and a high dose of propofol. After struggling for 9 months, he dramatically recovered after ketogenic diet therapy.

Conclusion:

Ketogenic diet therapy may be an important tool to help cure AERRPS.     

125I seeds implantation for treating residual hepatocellular carcinoma located beneath the diaphragm after transcatheter arterial chemoembolization

PurposeThe effect of ¹²⁵I seed implantation for the treatment of local residual tumor of hepatocellular carcinoma located beneath the diaphragm (HCC-LBD) after transcatheter arterial chemoembolization (TACE) has not yet been reported. This retrospective study was performed to evaluate the safety and efficacy of ¹²⁵I seeds implantation (ISI) for the treatment of residual HCC-LBD after TACE.Methods and MaterialsA total of 18 patients treated with ISI between August 2012 and March 2018 for residual HCC-LBD after single or multiple TACE were enrolled. Local control, survival, and postoperative complications were analyzed retrospectively. Overall followup time was displayed by survival curves.ResultsThe 18 patients received a total of 20 ISI treatments. The total number of seeds implanted was 650, with a mean of 36 ± 13 seeds per patients (range, 20–70). Mean D90 was 123 Gy. Complete response + partial response (CR + PR) was documented in 14, 16, and 16 of patients at 3, 6, and 12 months after implantation, respectively. In four patients, seeds implantation was performed through the diaphragm; two of these patients developed small pneumothoraces. Pulmonary compression of pneumothorax is less than 30% combined with a little blood in sputum, no chest tightness, shortness of breath, all symptoms subsided without interventions, and the patients were discharged after observation for 2 days. After the procedure, routine blood examination and liver and kidney function were normal.ConclusionThe combination of TACE with ISI appears to be a safe and efficient treatment for residual HCC-BLD.Implications for PracticeThis study evaluated the feasibility, safety, and short-term efficacy of ISI for local residual tumor of hepatocellular carcinoma located beneath the diaphragm (HCC-LBD) after TACE. Results suggest that residual tumor of HCC after TACE located in the posterosuperior part of the liver (segments seven and eight), laparoscopic liver resection, and alblation is difficult to perform and that as a supplement treatment, ¹²⁵I seeds implantation is safe and easy accessible. TACE combined with ¹²⁵I seeds has excellent local control effectiveness, and long-term efficacy and survival benefit still need to be more comprehensively evaluated.     

碘-125粒子组织间植入治疗恶性肿瘤的效果

目的 评价组织间植入碘-125(¹²⁵I)粒子治疗恶性肿瘤的临床价值。方法 27例恶性肿瘤患者,其中肝癌肺转移10例、原发性肝癌4例、肝癌椎体转移3例、结肠癌肺转移3例、胰腺癌3例、肺癌2例、肝癌腹壁转移1例、十二指肠乳头癌术后局部复发并不全肠梗阻1例,在CT导向下植入¹²⁵I粒子,利用治疗计划系统(TPS)确定植入粒子的数量及位置,术后2个月复查CT评估疗效。结果 27例中,完全缓解(CR)5例,部分缓解(PR)13例,稳定(SD)7例,进展(PD)2例,总有效率66.7%,无严重并发症发生。结论 碘-125粒子植入治疗恶性肿瘤安全、微创,近期疗效肯定。     

125I粒籽植入治疗辐射防护及关键控制技术探讨

目的 探讨碘-125（¹²⁵I）放射性粒籽植入治疗过程中可能存在的放射性职业病危害因素及辐射水平,探讨关键控制技术。方法 以5家开展¹²⁵I粒籽植入治疗项目的医疗机构为研究对象,采用放射卫生学现场调查、工作场所辐射防护水平检测、人员个人剂量监测等方法,调查粒籽植入涉源工作场所及相关人员的辐射水平;结合源项分析及放射卫生管理经验,根据危害分析与关键控制点（HACCP）的原理,探讨¹²⁵I粒籽植入治疗过程的关键控制点。结果 不同涉源场所中粒籽植入源运输包装、粒籽植入治疗室和专用病房工作场所各关注点的周围剂量当量率为本底~1.80 μSv/h（病房门处）,均小于2.5 μSv/h;35名放射工作人员全年个人剂量监测结果为0.20~1.80 mSv,平均为0.42 mSv。结论 不同涉源场所的辐射水平及人员的受照剂量均符合国家标准限值的要求;应根据关键控制措施,对¹²⁵I放射性粒籽植入治疗过程的关键环节予以控制。     

Formulation and in vivo assessment of terconazole-loaded polymeric mixed micelles enriched with Cremophor EL as dual functioning mediator for augmenting physical stability and skin delivery

The aim of the current study was to formulate terconazole (TCZ) loaded polymeric mixed micelles (PMMs) incorporating Cremophor EL as a stabilizer and a penetration enhancer. A 2³ full factorial design was performed using Design-Expert® software for the optimization of the PMMs which were formulated using Pluronic P123 and Pluronic F127 together with Cremophor EL. To confirm the role of Cremophor EL, PMMs formulation lacking Cremophor EL was prepared for the purpose of comparison. Results showed that the optimal PMMs formulation (F7, where the ratio of total Pluronics to drug was 40:1, the weight ratio of Pluronic P123 to Pluronic F127 was 4:1, and the percentage of Cremophor EL in aqueous phase was 5%) had a high micellar incorporation efficiency (92.98?±?0.40%) and a very small micellar size (33.23?±?8.00?nm). Transmission electron microscopy revealed that PMMs possess spherical shape and good dispersibility. The optimal PMMs exhibited superior physical stability when compared with the PMMs formulation of the same composition but lacking Cremophor EL. Ex vivo studies demonstrated that the optimal PMMs formula markedly improved the dermal TCZ delivery compared to PMMs lacking Cremophor EL and TCZ suspension. In addition, it was found that the optimal PMMs exhibited a greater extent of TCZ deposition in the rat dorsal skin relative to TCZ suspension. Moreover, histopathological studies revealed the safety of the optimal PMMs upon topical application to rats. Consequently, PMMs enriched with Cremophor EL, as a stable nano-system, could be promising for the skin delivery of TCZ.