Theta-phase closed-loop stimulation induces motor paradoxical responses in the rat model of Parkinson disease

Background

High-frequency deep brain stimulation (DBS) has become a widespread therapy used in the treatment of Parkinson's Disease (PD) and other diseases. Although it has proved beneficial, much recent attention has been centered around the potential of new closed-loop DBS implementations.

The dopaminergic system dynamic in the time perception: a review of the evidence

Dopaminergic system plays a key role in perception, which is an important executive function of the brain. Modulation in dopaminergic system forms an important biochemical underpinning of neural mechanisms of time perception in a very wide range, from milliseconds to seconds to longer daily rhythms. Distinct types of temporal experience are poorly understood, and the relationship between processing of different intervals by the brain has received little attention. A comprehensive understanding of interval timing functions should be sought within a wider context of temporal processing, involving genetic aspects, pharmacological models, cognitive aspects, motor control and the neurological diseases with impaired dopaminergic system. Particularly, an unexplored question is whether the role of dopamine in interval timing can be integrated with the role of dopamine in non-interval timing temporal components. In this review, we explore a wider perspective of dopaminergic system, involving genetic polymorphisms, pharmacological models, executive functions and neurological diseases on the time perception. We conclude that the dopaminergic system has great participation in impact on time perception and neurobiological basis of the executive functions and neurological diseases.     

Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men

Neurological disorders are a major threat to public health. Stem cell‐based regenerative medicine is now a promising experimental paradigm for its treatment, as shown in pre‐clinical animal studies. Initial attempts have been on the replacement of neuronal cells only, but glial progenitors (GPs) are now becoming strong alternative cellular therapeutic candidates to replace oligodendrocytes and astrocytes as knowledge accumulates about their important emerging role in various disease processes. There are many examples of successful therapeutic outcomes for transplanted GPs in small animal models, but clinical translation has proved to be challenging due to the 1,000‐fold larger volume of the human brain compared to mice. Human GPs transplanted into the mouse brain migrate extensively and can induce global cell replacement, but a similar extent of migration in the human brain would only allow for local rather than global cell replacement. We review here the mechanisms that govern cell migration, which could potentially be exploited to enhance the migratory properties of GPs through cell engineering pre‐transplantation. We furthermore discuss the (dis)advantages of the various cell delivery routes that are available, with particular emphasis on intra‐arterial injection as the most suitable route for achieving global cell distribution in the larger brain. Now that therapeutic success has proven to be feasible in small animal models, future efforts will need to be directed to enhance global cell delivery and migration to make bench‐to‐bedside translation a reality.     

Hypogonadotrophic hypogonadism,delayed puberty and risk for neurodevelopmental disorders

Hypogonadotrophic hypogonadism (HH) is a rare disorder that manifests absent puberty and infertility. Genetic syndromes with hypogonadism, such as Klinefelter syndrome, are associated with an increased risk of neurodevelopmental disorders (NDDs). However, it is not clear whether patients with HH or transient delayed puberty in general, have an increased risk of NDDs. We performed a register‐based study on a national cohort of 264 patients with HH and 7447 patients diagnosed with delayed puberty that was matched with 2640 and 74 470 controls, respectively. The outcome was defined as having any of the following NDD diagnoses: (i) autism spectrum disorder (ASD); (ii) attention deficit hyperactivity disorder (ADHD); or (iii) intellectual disability (ID). Additional sensitivity analyses were performed to control for different parental and birth variables, as well as diagnosed malformation syndromes and chromosomal anomalies (ie, Down’s and Turner syndromes). Patients with HH had increased risk for being diagnosed with ASD (odds ratio [OR] = 5.7; 95% confidence interval [CI] = 2.6‐12.6), ADHD (OR = 3.0; 95% CI = 1.8‐5.1) and ID (OR = 18.0; 95% CI = 8.9‐36.3) compared to controls. Patients with delayed puberty also had a significantly increased risk of being diagnosed with an NDD. These associations remained significant after adjustments. This is the first study to demonstrate a significant association between HH, delayed puberty and NDDs in a population‐based cohort. Clinicians should be aware of the overlap between these disorders. Further studies should explore the mechanisms behind these associations.     

Cerebral Venous Sinus Thrombosis as a Rare Complication of Systemic Lupus Erythematosus: Subgroup Analysis of the VENOST Study

AimSystemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics.Material and MethodAmong the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded.ResultsIn total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up.ConclusionsSLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings.     

急性孤立性脑桥梗死神经功能缺损进展的危险因素分析

目的 探讨急性孤立性脑桥梗死（acute isolated pontine infarction,AIPI）神经功能缺损进展的危险 因素、病因分型及预后。 方法 回顾性分析2015年1月-2018年6月在西安交通大学第二附属医院神经内科住院的AIPI患者临 床资料,根据其是否存在神经功能缺损进展,将患者分为进展组与非进展组。记录两组患者一般资 料、病因分型、椎-基底动脉延长扩张症（vertebrobasilar dolichoectasia,VBD）的发生率及预后,通过多 元逻辑回归分析确定AIPI神经功能缺损进展的危险因素。 结果 最终纳入122例AIPI患者,进展组28例（23.0%）,非进展组94例（77.0%）。进展组在糖尿病 患病率、入院时吞咽障碍发生率及出院时mRS评分均高于非进展组,差异具有统计学意义。进展组 病因分型中基底动脉分支动脉疾病（basilar artery branch disease,BABD）有16例（57.1%）,小动脉疾病 （small artery disease,SAD）有2例（7.1%）,大动脉闭塞性疾病（large artery occlusive disease,LAOD）有 10例（35.7%）,进展组与非进展组差异有统计学意义（χ 2=8.739,P =0.013）。进展组VBD的发生率为 25.0%（7/28）,高于非进展组的13.8%（13/94）,但两组比较差异无统计学意义（P =0.267）。相比非 进展组,进展组不良预后比例显著增加（46.4% vs 10.6%,P <0.001）。Logistic回归分析显示,吞咽障 碍是AIPI神经功能缺损进展的独立危险因素（OR 4.610,95%CI 1.461～14.546,P =0.009）。 结论 AIPI的患者,当存在糖尿病、吞咽障碍、VBD、病因分型BABD时可能更容易出现神经功能缺损 进展;吞咽障碍是AIPI神经功能缺损进展的独立危险因素;发生神经功能缺损进展的AIPI患者预后 不良的发生率增高。