帕金森病患者便秘治疗的研究进展

便秘是帕金森病最常见的非运动症状之一,不仅严重影响患者的生活质量,而且会对左旋多巴的吸收产生负面影响,严重的便秘甚至会引发帕金森病的恶性综合征.帕金森病患者的便秘症状可以通过增加饮水量、在饮食中添加益生菌,改善肠道菌群,口服聚乙二醇、鲁比前列酮、β-受体阻滞剂等药物,注射肉毒毒素,应用功能性磁刺激、腹部按摩等物理治疗获...     

肠道菌群与帕金森病

帕金森病(Parkinson disease,PD)是一种α突触核蛋白(alpha-synuclein,α-syn)异常沉积于脑内、外多神经系统的退行性疾病,除了典型的运动症状外,还有许多非运动症状,特别是胃肠道症状如肠道蠕动慢、吸收差、便秘等是常见的PD非运动症状。有研究表明肠道菌群失衡会导致α突触核蛋白在肠道神经系统内沉积,且沿脑-肠轴上升迁移至脑内并沉积,最后导致PD发生,故有学者推测PD的早期发病可能在肠道,是由菌群失调所致。因此,探索脑-肠道-微生物轴的相互作用关系,明确肠道菌群改变与PD发病的因果关系及作用机制,将有助于深刻理解PD的发病机制,并可能为PD的预防和未来治疗提供新的证据。     

肠道微生物与常见中枢神经系统疾病相关性的研究进展

肠道微生物不仅局限作用于胃肠道,可以通过脑肠轴对大脑功能产生重要影响.肠道微生物结构与功能的改变与阿茨海默病、帕金森病、多发性硬化、脑卒中等一系列常见中枢神经系统疾病密切相关,通过改善肠道微生物的微生态疗法有望成为预防和治疗中枢神经系统疾病的有效途径.现对近年来肠道微生物与常见中枢神经系统疾病的相关研究进展进行综述.     

帕金森病患者肠道菌群变化及以其为干预靶点的研究进展

帕金森病(Parkinson disease,PD)患者肠道菌群组成发生明显变化.目前研究初步结果显示,通过粪菌移植和补充益生菌、益生元等途径可调控PD肠道菌群,改善患者震颤、便秘、焦虑、抑郁、睡眠障碍等症状,但其作用确切机制尚未完全阐明,且其长期有效性和安全性亦有待明确.现就近年来有关PD患者肠道菌群变化及以此为干预...     

肠道微生物-大脑轴与孤独症谱系障碍北大核心CSCD

孤独症谱系障碍(ASD)患病率不断攀升,且预后差,致残率高,给家庭和社会带来巨大的经济负担,已成为全世界备受关注的疾病之一。目前该病病因尚不明确,治疗主要为教育训练。由于缺乏针对性强的精准治疗方法,治疗效果差强人意。近年来的数项研究证实,与典型发育的对照组(typical development children)相比,ASD患者肠道微生物有改变,存在肠道菌群失调,9%~91%的ASD患儿有胃肠道疾病症状,约半数伴有腹泻或便秘。若干研究证实了益生菌通过改善肠道菌群治疗ASD的疗效,益生菌既可缓解其胃肠道症状,也可改善部分行为问题,我们将就ASD的病因和发病机制以及目前ASD治疗方面的进展进行综述。     

益生菌治疗心境障碍机制的研究进展

近年来,心境障碍患者的肠道菌群紊乱逐渐受到人们的关注。肠道菌群经微生物 - 肠 - 脑（MGB）轴沟通中枢神经系统实现双向调节,影响人的认知、情绪和行为。益生菌及其产物重塑肠道 微生态,改善免疫和内分泌系统功能,恢复神经递质水平。因此,应用益生菌调节失衡的肠道菌群,恢 复紊乱的 MGB 轴正成为心境障碍的辅助疗法。但目前益生菌疗法仍存在一些问题,如菌株之间的差异 性、肠道菌群组成的异质性等。未来需要进行更多试验以明确不同菌株作用机制,从而对不同亚型心 境障碍患者针对性地使用益生菌,完善治疗策略。     

外周炎症和中枢炎症在帕金森病发病机制中的作用

帕金森病(PD)是第二常见的神经退行性疾病,主要临床症状为运动障碍,给患者带来极大困扰。近年来大量研究表明,PD与外周和中枢炎症密切相关。PD患者首先出现便秘等运动前症状,肠道屏障功能障碍和肠道微生物失调加速肠神经胶质细胞激活、α-突触核蛋白聚集以及外周免疫细胞增殖,产生各种促炎细胞因子和趋化因子。大脑内,各种病原体相关分子模式(PAMPs)和组织相关分子模式(DAMPs)激活小胶质细胞,主要通过TLRSNF-κB-NLRP3信号通路促进NLRP3炎性小体组装,促炎因子释放,最终导致多巴胺能神经元死亡。外周促炎因子使血脑屏障通透性增加,淋巴细胞、单核/巨噬细胞等外周免疫细胞进一步加剧中枢神经炎症。文中总结了外周炎症和中枢炎症在PD发病中的作用,为今后治疗PD提供可能的治疗靶点。     

肠道菌群在强迫症治疗中的研究进展

强迫症是一种病因未明的致残性精神障碍, 其发生发展过程与肠道菌群的关联尚未被完全阐明。虽然强迫症的确切发病机制尚不清楚, 但现有证据表明脑肠轴通过免疫炎症、神经递质及内分泌等多条通路参与强迫症的发生发展。本文综述了肠道微生物群参与强迫症病理生理学的新证据及其作为新的治疗手段的潜力, 同时总结了目前脑肠轴研究的主要研究方法和不足。探讨了益生菌和粪便移植等微生物重组策略在强迫症治疗中的潜力和挑战, 并对未来的研究方向进行了展望, 期待通过对脑肠轴的深入研究能够为强迫症的防治提供新的靶点和方向。     

肠道微生物参与帕金森病发生发展的研究进展

帕金森病是一种由多种因素导致的临床综合征,主要表现为多巴胺能神经元丢失和α-突触核蛋白异常聚集两方面。肠道微生物异常代谢产物可作为炎症因子通过循环途径进入大脑引起线粒体功能障碍,导致多巴胺神经元丢失,也可作为信号因子通过脑-肠-微生物组轴损伤中枢神经系统,并造成α-突触核蛋白错误折叠。本文综述了肠道微生物及其代谢产物在帕金森病中的临床应用和研究进展,以期为帕金森病患者的治疗提供新的思路。     

粪菌移植治疗中枢神经系统疾病的研究进展

中枢神经系统疾病除了神经系统相关症状外，常伴随胃肠道症状，在不同疾病患者体内可观察到相应肠道菌群失调现象。肠道菌群及代谢产物可通过外周神经、免疫等途径参与中枢神经系统活动，肠道菌群失调与阿尔兹海默病、帕金森病、肌萎缩性脊髓侧索硬化、多发性硬化等多种中枢神经系统疾病的发生发展密切相关，有研究证明，模型动物或患者在接受粪菌移植治疗后症状改善。该文就粪菌移植治疗中枢神经系统疾病中的研究进展进行综述。     

Cognitive Impairment in Parkinson's Disease without Dementia: Subtypes and Influences of Age

Background and Purpose

Cognitive impairments are common in Parkinson''s disease (PD), although the severity of these impairments does not significantly impair the patient''s daily activities. The aim of this study was to determine the frequency of mild cognitive impairment (MCI) of Parkinson''s disease (PDMCI) and its subtypes in nondemented PD patients. We also evaluated the influence of age on the pattern of subtypes of PDMCI.

Methods

A total of 141 consecutive, nondemented PD patients underwent a comprehensive neuropsychological assessment covering the five cognitive domains: attention, language, visuospatial, memory, and executive functions. PDMCI was defined as impaired performance in at least one of these five cognitive domains. The influence of age on the distribution of subtypes of PDMCI was assessed by comparing patients in two groups dichotomized according to their age at assessment (younger vs. older).

Results

Fifty-seven (40.4%) of the nondemented PD patients had an impairment in at least one domain, and were therefore considered as having PDMCI. The age at assessment and age at disease onset were significantly higher in the PDMCI patients. The amnestic type of PDMCI was the most frequent, followed by the visuospatial, linguistic, executive, and attention types in that order. The frequency of PDMCI was higher for all subtypes in the older group; the domain that was influenced the most by age was executive function.

Conclusions

MCI was common in PD and the subtypes were diverse. Age was found to be an important risk factor for the development of PDMCI, particularly for the executive subtype. These results indicate that the concept of MCI should be introduced in PD.     

Steroid-responsive encephalopathy in autoimmune thyroiditis: Clinical spectrum and MRI observations in three cases

Hashimoto''s encephalopathy (H.E.) is probably of autoimmune etiology, and manifests with seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms, myoclonus. It is presumed to be autoimmune in origin with high serum titers of antithyroid peroxidase antibodies (anti-TPA). Thyroid function might often be normal. The diagnosis is arrived at by excluding other toxic, metabolic and infectious causes of encephalopathies, supportive clinical profile, elevated thyroid antibodies and optimum steroid response. We present the characteristic phenotypic manifestations, magnetic resonance imaging and electroechography observations and response to immunomodulation with follow-up in three cases of H.E. All the three cases manifested with subacute to chronic progressive encephalopathy, cerebellar dysfunction, seizures, behavioral abnormalities and oculomotor disturbances and had evidence of hypothyroidism, elevated titers of anti-TPA and positive thyroid anti-microsomal antibodies. Atypical and uncommon presentations are known. This report emphasizes that a high index of suspicion is often required in cases with “investigation negative encephalopathy” for early diagnosis of H.E.     

Scoliosis in Patients with Parkinson's Disease

Background and purpose

Scoliosis is more common in patients with Parkinson''s disease (PD) than in the general elderly population. We compared clinical characteristics between PD patients with and without scoliosis, to identify the relationship between the direction of scoliosis and the laterality of the dominant symptoms of PD. We also studied the associations between dopaminergic pharmacotherapy and scoliosis (defined by a spinal curvature deviation of 10° or larger).

Methods

The study population comprised 97 patients (42 men and 55 women) with idiopathic PD. All of the patients submitted to a whole-spine scanograph to allow measurement of the degree of scoliosis by Cobb''s method.

Results

True scoliosis was found in 32 of the 97 PD patients, and was observed more frequently in women than in men (28 vs. 4, respectively; p=0.006). The age of patients without scoliosis was significantly lower than that of those with scoliosis (66.5±9.2 years vs. 72.8±7.3 years, respectively, mean±SD, p<0.001). There was no correlation between PD symptom laterality and scoliosis. The rate of occurrence of scoliosis did not differ between de novo and levodopa (L-dopa)-treated patients.

Conclusions

We suggest that neither L-dopa treatment nor the laterality of the initial symptoms of PD is related to the appearance of scoliosis.     

Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study

Emerging evidence suggests that Alzheimer''s disease (AD) and Parkinson''s disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer''s disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD<PDD) and right frontal cortex (PDD<AD). In conclusion, the pattern of cerebral hypoperfusion is very similar in AD and PDD. This suggests closely linked mechanisms of neurodegeneration mediating the evolution of dementia in both conditions.     

帕金森操康复训练的临床疗效观察

目的探讨帕金森健康操对帕金森病患者运动功能和日常生活能力的影响。方法选取2013年4月至2014年7月期间我院收治的帕金森病患者38例。分为两组:治疗组给予临床常规药物治疗及常规康复治疗,并在此基础上教授帕金森健康操,每天2 h;对照组仅给予临床常规药物治疗及常规康复治疗。治疗5月及14月后观察疗效。结果两组治疗5月后UPDRSⅡ评分和UPDRSⅢ评分均较治疗前降低,差异具有统计学意义(P0.05);治疗组在治疗14月后,与治疗前比较降低更加显著(P0.01)。治疗组在治疗14月后与治疗5月后比较也有明显降低,差异具有统计学意义(P0.05)。治疗5月后和治疗14月后治疗组与对照组比较,差异均有统计学意义(P0.05)。结论帕金森健康操能提高帕金森病患者的运动功能,改善患者的日常生活活动能力,特别是长期预后具有较好的临床效果。     

Biomarkers Predicting Alzheimer's Disease in Cognitively Normal Aging

The pathophysiologic process of Alzheimer''s disease (AD) begins years before the diagnosis of clinical dementia. This concept of preclinical AD has arisen from the observation of AD pathologic findings such as senile plaques and neurofibrillary tangles in the brains of people who at the time of death had normal cognitive function. Recent advances in biomarker studies now provide the ability to detect the pathologic changes of AD, which are antecedent to symptoms of the illness, in cognitively normal individuals. Functional and structural brain alterations that begin with amyloid-β accumulation already show the patterns of abnormality seen in individuals with dementia due to AD. The presence of preclinical AD provides a critical opportunity for potential interventions with disease-modifying therapy. This review focuses on the studies of antecedent biomarkers for preclinical AD.     

Sundown syndrome in persons with dementia: an update

"Sundowning" in demented individuals, as distinct clinical phenomena, is still open to debate in terms of clear definition, etiology, operationalized parameters, validity of clinical construct, and interventions. In general, sundown syndrome is characterized by the emergence or increment of neuropsychiatric symptoms such as agitation, confusion, anxiety, and aggressiveness in late afternoon, in the evening, or at night. Sundowning is highly prevalent among individuals with dementia. It is thought to be associated with impaired circadian rhythmicity, environmental and social factors, and impaired cognition. Neurophysiologically, it appears to be mediated by degeneration of the suprachiasmatic nucleus of the hypothalamus and decreased production of melatonin. A variety of treatment options have been found to be helpful to ameliorate the neuropsychiatric symptoms associated with this phenomenon: bright light therapy, melatonin, acetylcholinesterase inhibitors, N-methyl-d-aspartate receptor antagonists, antipsychotics, and behavioral modifications. To decrease the morbidity from this specific condition, improve patient's well being, lessen caregiver burden, and delay institutionalization, further attention needs to be given to development of clinically operational definition of sundown syndrome and investigations on etiology, risk factors, and effective treatment options.