Li-jun Zuo

Nonmotor symptoms in patients with Parkinson disease: A cross-sectional observational study.

AbstractParkinson disease (PD) is usually accompanied by numerous nonmotor symptoms (NMS), such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunctions, and sensory disturbances. However, it is not clear that the factors influencing the occurrence of NMS and its sequence with motor symptoms (MS).We conducted comprehensive assessments of NMS by using 13 scales in 1119 PD patients.A total of 70.8% PD patients present NMS. Olfactory dysfunction tends to occur in PD patients with older age, more severe depression, sleep problems, and autonomic dysfunctions. Older patients are more likely to have olfactory dysfunction before MS than younger patients. Rapid eye movement behavior disorder is more prone to happen in patients with older age, older onset age, more severe depression, sleep problems, and autonomic dysfunctions. Patients with rapid eye movement behavior disorder before MS are older in onset age than after group.Olfactory dysfunction, constipation, rapid eye movement behavior disorder, and depression, as early warning NMSs of PD, connected to each other. There is a clinical heterogeneity that older patients are more likely to have NMS before MS, while younger patients are opposite.

Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease

Fatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It included physical fatigue and mental fatigue. The potential mechanisms of mental fatigue involving serotonergic dysfunction and abnormal iron metabolism are still unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients into fatigue group and non-fatigue group, and detected the levels of serotonin, iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly decreased and the levels of iron and transferrin are dramatically increased in fatigue group. In fatigue group, mental fatigue score is negatively correlated with 5-HT level in CSF, and positively correlated with the scores of depression and excessive daytime sleepiness, and disease duration, also, mental fatigue is positively correlated with the levels of iron and transferrin in CSF. Transferrin level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5-HT and transferrin are markedly decreased in fatigue group; mental fatigue score exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in both central and peripheral systems may be correlated with mental fatigue through abnormal iron metabolism. Depression, excessive daytime sleepiness and disease duration were the risk factors for mental fatigue of PD.

Excessive Iron and α-Synuclein Oligomer in Brain are Relevant to Pure Apathy in Parkinson Disease.

Objectives: To investigate the demographic features, clinical features, and potential mechanism in patients with Parkinson disease (PD) with pure apathy. Method: A total of 145 patients with PD without depression and dementia and 30 age-matched controls were consecutively recruited. Patients with PD were evaluated by Apathy Scale (AS), scales for motor symptoms and quality of life. The levels of iron, oxidative and neuroinflammatory factors, α-synuclein oligomer, and dopamine in cerebrospinal fluid (CSF) from patients with PD and controls were detected by enzyme-linked immunosorbent assay, chemical colorimetric method, and high-performance liquid chromatography. Comparisons between PD with pure apathy and with no pure apathy groups and correlation between AS score and the levels of above factors were analyzed. Results: There were 64 (44.14%) cases in PD-apathy group. The PD-apathy group had older age, (97.81 ± 10.82) years versus (61.86 ± 10.80) years, and severer quality of life (P < .05). The PD-apathy and PD without apathy groups presented no remarkable differences in motor symptoms (P > .05). The levels of iron, hydroxyl radical (·OH), hydrogen peroxide (H2O2), and α-synuclein oligomer in CSF in PD-apathy group were significantly higher than that in PD without the apathy group (P < .05). In patients with PD, the AS score was positively correlated with the levels of iron, ·OH, H2O2 and α-synuclein oligomer in CSF (r = 19.838, .063, 1.046, and 0.498, respectively, P < .05). In PD-apathy group, iron level was positively correlated with ·OH level (r = .011, P < .05), and H2O2 level was positively correlated with α-synuclein oligomer level in CSF (r = .045, P < .05). Conclusion: Patients with PD had high prevalence of pure apathy. Patients with PD having pure apathy had older age. Pure apathy reduced quality of life for patients without worsening motor function. Excessive iron and α-synuclein oligomer in brain commonly contributed to pure apathy of PD through potential mechanism of oxidative stress.

Restless legs syndrome in Parkinson disease: Clinical characteristics, abnormal iron metabolism and altered neurotransmitters

Relationships among clinical characteristics, iron metabolism and neurotransmitters in Parkinson disease (PD) patients with restless legs syndrome (RLS) remains unclear. We divided 218 patients into PD with and with no RLS (PD-RLS and PD-NRLS) groups by RLS-rating scale (RLS-RS) score. Motor and non-motor symptoms were rated by related scales. Iron and related proteins, and neurotransmitters in cerebrospinal fluid (CSF) and serum were measured. PD-RLS frequency was 40.37%. PD-RLS group had longer duration, higher stage and scores of motor symptoms, depression, anxiety, sleep disorders, fatigue and apathy, and increased transferrin and decreased iron, ferritin, dopamine (DA) and 5-hydroxytryptamine (5-HT) in CSF. In CSF of PD-RLS group, RLS-RS score was positively correlated with transferrin level and negatively correlated with iron and ferritin levels; RLS-RS score was negatively correlated with DA and 5-HT levels; transferrin level was negatively correlated with DA and 5-HT levels, and ferritin level was positively correlated with DA level. In serum, PD-RLS group had decreased iron and transferrin levels, which were negatively correlated with RLS-RS score. PD-RLS was common and severer in motor and some non-motor symptoms. Iron deficiency induced by its metabolism dysfunctions in peripheral and central systems might cause PD-RLS through decreasing brain DA and 5-HT.

Screening for cognitive impairment with the Montreal Cognitive Assessment in Chinese patients with acute mild stroke and transient ischaemic attack: a validation study

Objective We aimed to establish the cut-off point of the Montreal Cognitive Assessment (MoCA-Beijing) in screening for cognitive impairment (CI) within 2 weeks of mild stroke or transient ischaemic attack (TIA). Methods A total of 80 acute mild ischaemic stroke patients and 22 TIA patients were recruited. They received the MoCA-Beijing and a formal neuropsychological test battery. CI was defined by 1.5 SD below the established norms on a formal neuropsychological test battery. Results Most stroke and TIA patients were in their 50s (53.95±11.43 years old), with greater than primary school level of education. The optimal cut-off point for MoCA-Beijing in discriminating patients with CI from those with no cognitive impairment (NCI) was 22/23 (sensitivity 85%, specificity 88%, positive predictive value=91%, negative predictive value=80%, classification accuracy=86%). The predominant cognitive deficits were characteristic of frontal-subcortical impairment, such as visuomotor speed (46.08%), attention/executive function (42.16%) and visuospatial ability (40.20%). Conclusions A MoCA-Beijing cut-off score of 22/23 is optimally sensitive and specific for detecting CI after mild stroke, and TIA in the acute stroke phase, and is recommended for routine clinical practice.

Minimally Toxic Dose of Lipopolysaccharide and α-Synuclein Oligomer Elicit Synergistic Dopaminergic Neurodegeneration: Role and Mechanism of Microglial NOX2 Activation

The aim of this study is to investigate the role and mechanism of microglial NOX2 activation in minimally toxic dose of LPS and Syn-elicited synergistic dopaminergic neurodegeneration. NOX2+/+ and NOX2−/− mice and multiple primary cultures were treated with LPS and/or Syn in vivo and in vitro. Neuronal function and morphology were evaluated by uptake of related neurotransmitter and immunostaining with specific antibody. Levels of superoxide, intracellular reactive oxygen species, mRNA and protein of relevant molecules, and dopamine were detected. LPS and Syn synergistically induce selective and progressive dopaminergic neurodegeneration. Microglia are functionally and morphologically activated, contributing to synergistic dopaminergic neurotoxicity elicited by LPS and Syn. NOX2−/− mice are more resistant to synergistic neurotoxicity than NOX2+/+mice in vivo and in vitro, and NOX2 inhibitor protects against synergistic neurotoxicity through decreasing microglial superoxide production, illustrating a critical role of microglial NOX2. Microglial NOX2 is activated by LPS and Syn as mRNA and protein levels of NOX2 subunits P47and gp91 are enhanced. Molecules relevant to microglial NOX2 activation include PKC-σ, P38, ERK1/2, JNK, and NF-КBP50 as their mRNA and protein levels are elevated after treatment with LPS and Syn. Combination of exogenous and endogenous environmental factors with minimally toxic dose synergistically propagates dopaminergic neurodegeneration through activating microglial NOX2 and relevant signaling molecules, casting a new light for PD pathogenesis.

Phenotype of postural instability/gait difficulty in Parkinson disease: relevance to cognitive impairment and mechanism relating pathological proteins and neurotransmitters

Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected the levels of pathological proteins and neurotransmitters in CSF. TD group and PIGD group had significantly higher levels of total tau, tau phosphorylated at the position of threonine 181(P-tau181t), threonine 231, serine 396, serine 199 and lower β amyloid (Aβ)1–42 level in CSF than those in control group; PIGD group had significantly higher P-tau181t level and lower Aβ1–42 level than those in TD group. In PD group, PIGD severity was negatively correlated with MoCA score and Aβ1–42 level in CSF, and positively correlated with Hoehn-Yahr stage and P-tau181t level in CSF. In PIGD group, PIGD severity was negatively correlated with homovanillic acid (HVA) level in CSF, and HVA level was positively correlated with Aβ1–42 level in CSF. PIGD was significantly correlated with cognitive impairment, which underlying mechanism might be involved in Aβ1–42 aggregation in brain and relevant neurochemical disturbance featured by the depletion of HVA in CSF.

Iron deposition in substantia nigra: abnormal iron metabolism, neuroinflammatory mechanism and clinical relevance

Parkinson disease (PD) is associated with multiple factors, including iron, which is demonstrated to deposit excessively in PD brains. We detected iron deposition by susceptibility weighted image (SWI) and measured the levels of iron metabolism-related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum of PD patients and control subjects. Clinical symptoms of PD were evaluated by series of rating scales. Relationships among above factors were analyzed. Results showed that corrected phase (CP) value of substantia nigra (SN) was significantly decreased in PD group compared to control group, hence, SN was the main region with excessive iron deposition. In PD group, ferritin was significantly elevated in CSF and reduced in serum compared to control group, and levels of ferritin in CSF and serum were both significantly and positively correlated with CP value of SN, thus, abnormal iron metabolism in central and peripheral systems was associated with iron deposition. CP value of SN in PD group was significantly and negatively correlated with interleukin-1β level in CSF, so interleukin-1β might be a neuroinflammatory factor produced by excessive iron in SN. Iron deposition in SN was significantly correlated with motor symptoms and part of non-motor symptoms of PD.

Ipsiversive ictal eye deviation in inferioposterior temporal lobe epilepsy—Two SEEG cases report

BackgroundVersive seizure characterized by conjugate eye movement during epileptic seizure has been considered commonly as one of the most valuable semiological signs for epilepsy localization, especially for frontal lobe epilepsy. However, the lateralizing and localizing significance of ictal eye deviation has been questioned by clinical observation of a series of focal epilepsy studies, including frontal, central, temporal, parietal and occipital epilepsy.Case presentationTwo epileptic cases characterized by ipsiversive eye deviation as initial clinical sign during the habitual epileptic seizures are presented in this paper. The localization of the epileptogenic zone of both of the cases has been confirmed as inferioposterior temporal region by the findings of ictal stereoelectroencephalography (SEEG) and a good result after epileptic surgery. Detailed analysis of the exact position of the key contacts of the SEEG electrodes identified the overlap between the location of the epileptogenic zone and human MT/MST complex, which play a crucial role in the control of smooth pursuit eye movement.ConclusionIpsiversive eye deviation could be the initial clinical sign of inferioposterior temporal lobe epilepsy and attribute to the involvement of human MT/MST complex, especially human MST which was located on the anterior/dorsal bank of the anterior occipital sulcus (AOS).

The Relationship between Cerebral White Matter Integrity and Cognitive Function in Mild Stroke with Basal Ganglia Region Infarcts

Mild stroke is a known risk factor for dementia. The relationship between cerebral white matter (WM) integrity and cognitive impairment (CI) in mild stroke patients with basal ganglia region infarcts is unknown. Total of 33 stroke patients and 19 age-matched controls underwent diffusion tensor imaging scans and a formal neuropsychological test battery. CI was defined as having a performance score 1.5 SD below the established norm. We compared the differences in Z-scores and Fraction Anisotropy (FA) values among controls, stroke with no CI (NCI) and stroke with CI groups. Multiple linear regressions were performed between FA values in affected regions and neuropsychological tests in stroke patients. The majority of stroke patients were in their 50s (56.90 ± 9.23 years). CI patients exhibited a significantly decreased Z score in visual delayed memory and remarkably decreased FA values in the right external capsule and right fornix (FWE-corrected) compared with NCI patients and controls. In stroke patients, the FA value in the right fornix was positively correlated with delayed visual memory. Mild stroke with basal ganglia region infarcts may be related to widespread abnormality of WM integrity. The lower WM integrity in the right fornix may be a marker of impaired delayed visual memory.