Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

BACKGROUND: Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. METHODS: PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. RESULTS: PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P < 0.05). Compared with PDSN- group, the levels of transferrin and light-ferritin in serum and iron level in CSF were significantly elevated (P < 0.05), but ferroportin level in CSF was significantly decreased in PDSN+ group (P < 0.05). CONCLUSIONS: PD patients with hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

Influence of Marital Status on the Quality of Life of Chinese Adult Patients with Epilepsy.

BACKGROUND: Epilepsy is a chronic disorder characterized by recurrent seizures and has significant psychological and social consequence for everyday living. Epilepsy affects various aspects of ones' social life. The present study aimed to investigate the influence of marital status on the quality of life of adult Chinese patients with epilepsy. METHODS: This study surveyed 805 Chinese adults who have been clinically diagnosed with epilepsy for longer than 1 year in 11 hospitals in Beijing. In this survey, 532 (66.1%) participants were married. All of them completed the case report form with enquiries on demographic data, social factors, and illness. The marriage status of adult epileptic quality of life was the dependent variable, and demographic data and clinical data were independent variables, analyzed through the multiple linear regression analysis methods. The patients' quality of life was assessed using the Quality of Life in patients with Epilepsy-31 items (QOLIE-31) questionnaire, the Patient Health Questionnaire-9 items (PHQ-9), and the Generalized Anxiety Disorder-7 items (GAD-7). RESULTS: The PHQ-9 and GAD-7 scores in the unmarried group (PHQ-9 = 6.0 and GAD-7 = 5.0) were significantly higher than that of the married group (PHQ-9 = 4.0 and GAD-7 =3.0). The scores of married adult patients with epilepsy on QOLIE (61.8 ± 15.3) and social function (70.9 ± 22.7) were higher than the scores of the unmarried patients aged between 20 and 44 years. The scores of married adult epileptics on the QOLIE (58.4 ± 14.6) and the energy/fatigue (62.1 ± 20.4) were higher than the scores of the unmarried patients (QOLIE = 58.4 ± 14.6 and the energy/fatigue = 62.1 ± 20.4) aged between 45 and 59 years. For the adult epilepsy patients, depression, anxiety, seizures within the last year, disease course, medical expense category, and marriage* age are negatively correlated with the quality of life. Occupation, educational level, and average monthly income are closely related to the quality of life. CONCLUSIONS: Married adult epileptic patients have better quality of life than that of unmarried adult patients in young and middle-aged age groups. Unmarried adult patients with epilepsy are more anxious and depressed than married adult patients.

Influence of Occupational Status on the Quality of Life of Chinese Adult Patients with Epilepsy.

BACKGROUND: Epilepsy is one of the most common serious neurological disorders. The present study aimed to investigate the influence of occupational status on the quality of life of Chinese adult patients with epilepsy. METHODS: This study surveyed 819 subjects clinically diagnosed with epilepsy for more than 1 year in 11 hospitals in Beijing; 586 were employed (71.55%). All subjects completed the case report form with inquiries on demographic data, social factors, and illness. The patients' quality of life was assessed using the quality of life in patients with epilepsy-31 items (QOLIE-31) questionnaire. RESULTS: The QOLIE-31 score in the employed group was significantly higher than that in the unemployed group. Furthermore, the scores in all the sections (overall quality of life, energy/fatigue, emotional well-being, seizure worry, cognition, social function, and medication effects) of the employed group were higher than those of the unemployed group. Both the employed and unemployed groups achieved the highest difference in social function. The QOLIE-31 score of students was higher than those of farmers and workers. Both the students and workers scored higher in the quality of life compared with the adult peasants living with epilepsy. The students and farmers showed significant differences in QOLIE-31 score, cognition, emotional well-being, overall quality of life, energy/fatigue, and social function. In contrast, no significant difference was noted in seizure worry and medication effects across the three different kinds of occupation. CONCLUSION: Occupational status might affect the quality of life of Chinese adult patients with epilepsy, and social function is the most important contributing factor.

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.

Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD.

OBJECTIVE: To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). METHODS: Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. RESULTS: (1) The frequency of PRBD in PD patients is 31.90%. (2) PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3) In CSF, levels of iron, transferrin, NO and IL-1ß in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL-1ß in PD group. Iron level is positively correlated with the levels of NO and IL-1ß in PD group. (4) In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. CONCLUSIONS: PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation.

Parkinson disease with REM sleep behavior disorder: features, α-synuclein, and inflammation.

OBJECTIVES: To investigate clinical features and potential mechanisms involving α-synuclein oligomer and inflammation in patients with Parkinson disease (PD) and probable REM sleep behavior disorder (PRBD). METHODS: We used the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) to evaluate patients with PD and classified each as PRBD or not probable (NPRBD). Data collection included demographic information and evaluation of clinical symptoms using a series of rating scales. We tested for α-synuclein oligomer and inflammatory factors in CSF and serum. Data analyses included comparisons between PRBD and NPRBD groups and correlation analyses among RBDSQ score and levels of the above factors. RESULTS: The frequency of PRBD in patients with PD was 30.67%. The PRBD group had longer disease duration, more advanced disease stage, more severe motor symptoms, and other more severe nonmotor symptoms, including depression, anxiety, and fatigue. Levels of α-synuclein oligomer in CSF and serum in the PRBD group were elevated compared with NPRBD and control groups. RBDSQ score was increased with the elevated α-synuclein oligomer level in CSF, interleukin 1ß and nitric oxide levels in CSF, and prostaglandin E2 level in serum in the PD group. The level of α-synuclein oligomer in CSF was enhanced with the deterioration of motor symptoms, and the elevated levels of interleukin 1ß, nitric oxide, and tumor necrosis factor α in CSF in the PRBD group. CONCLUSIONS: PRBD is common in patients with PD, especially those with longer disease duration and more severe motor and nonmotor symptoms. Elevated α-synuclein levels in CSF and serum may be correlated with PRBD through inflammation in central and peripheral nervous systems.

Potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment: a cross-sectional study.

BACKGROUND: Cognitive impairment strikingly reduces the quality of life of Parkinson's disease (PD) patients. Studies find that pathological proteins, neuroinflammatory factors and free radicals may involve in the pathogenesis of cognitive impairment of PD, however, results are inconclusive. METHODS: We recruited 62 PD patients and 31 healthy controls. PD patients were identified with cognitive impairment, including PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD) according to the diagnostic criteria for PD-MCI and PDD issued by Movement Disorder Society Task Force. The levels of pathological proteins, including ß-amyloid 1-42 (Aß1-42),Total-tau (T-tau) and phosphorelated tau (P-tau), neuroinflammatory factors,including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interferon-γ (INF-γ) and prostaglandin E2 (PGE2), free radicals, including hydroxyl radical (·OH), hydrogen peroxide (H2O2) and nitric oxide (NO) in cerebrospinal fluid(CSF) were detected. The levels of above factors in CSF were compared among healthy controls and patients with and without cognitive impairment. Correlation analyses were performed between Montreal Cognitive Assessment (MoCA) score and the levels of above factors in CSF. RESULTS: T-tau level in CSF from PD-CI patients are significantly elevated comparing with those without cognitive impairment and controls (P = 0.016 and 0.004, respectively). The levels of P-tau (S396) and · OH in PD-CI patients are significantly higher than controls (P = 0.001 and 0.014, respectively). IL-6 levels in PD-CI patients are strikingly enhanced comparing with those without cognitive impairment (P = 0.005). MoCA score is negatively correlated with the levels of T-tau (r = -0.340), P-tau (S396) (r = -0.448), IL-6 (r = -0.489) and · OH (r = -0.504) in PD-CI patients. CONCLUSIONS: Elevated levels of T-tau, P-tau (S396), IL-6 and · OH in CSF are significantly correlated with cognitive impairment in PD patients. This investigation may suggest the potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment.

Role and mechanism of microglial activation in iron-induced selective and progressive dopaminergic neurodegeneration.

Parkinson's disease (PD) patients have excessive iron depositions in substantia nigra (SN). Neuroinflammation characterized by microglial activation is pivotal for dopaminergic neurodegeneration in PD. However, the role and mechanism of microglial activation in iron-induced dopaminergic neurodegeneration in SN remain unclear yet. This study aimed to investigate the role and mechanism of microglial ß-nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activation in iron-induced selective and progressive dopaminergic neurodegeneration. Multiple primary midbrain cultures from rat, NOX2+/+ and NOX2-/- mice were used. Dopaminergic neurons, total neurons, and microglia were visualized by immunostainings. Cell viability was measured by MTT assay. Superoxide (O2·-) and intracellular reactive oxygen species (iROS) were determined by measuring SOD-inhibitable reduction of tetrazolium salt WST-1 and DCFH-DA assay. mRNA and protein were detected by real-time PCR and Western blot. Iron induces selective and progressive dopaminergic neurotoxicity in rat neuron-microglia-astroglia cultures and microglial activation potentiates the neurotoxicity. Activated microglia produce a magnitude of O2·- and iROS, and display morphological alteration. NOX2 inhibitor diphenylene iodonium protects against iron-elicited dopaminergic neurotoxicity through decreasing microglial O2·- generation, and NOX2-/- mice are resistant to the neurotoxicity by reducing microglial O2·- production, indicating that iron-elicited dopaminergic neurotoxicity is dependent of NOX2, a O2·--generating enzyme. NOX2 activation is indicated by the increased mRNA and protein levels of subunits P47 and gp91. Molecules relevant to NOX2 activation include PKC-σ, P38, ERK1/2, JNK, and NF-КBP65 as their mRNA and protein levels are enhanced by NOX2 activation. Iron causes selective and progressive dopaminergic neurodegeneration, and microglial NOX2 activation potentiates the neurotoxicity. PKC-σ, P38, ERK1/2, JNK, and NF-КBP65 are the potential molecules relevant to microglial NOX2 activation.