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1.
Cereb Cortex ; 33(4): 959-968, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35348637

RESUMO

OBJECTIVE: Previous studies have revealed that, compared with Parkinson's disease (PD) patients without freezing of gait (FoG), the ones with FoG showed greater prefrontal activation while doing lower-limb movements involving standing, walking and turning, which require both locomotor and balance control. However, the relation between FoG and pure locomotor control as well as its underlying mechanism remain unclear. METHODS: A total of 56 PD subjects were recruited and allocated to PD-FoG and PD-noFoG subgroups, and 34 age-matched heathy adults were included as heathy control (HC). Functional near-infrared spectroscopy was used to measure their prefrontal activation in a sitting lower-limb movement task, wherein subjects were asked to sit and tap their right toes as big and as fast as possible. RESULTS: Result of one-way ANOVA (Group: PD-FoG vs. PD-noFoG vs. HC) revealed greater activation in the right prefrontal cortex in the PD-FoG group than in the other 2 groups. Linear mixed-effects model showed consistent result. Furthermore, the right prefrontal activation positively correlated with the severity of FoG symptoms in PD-FoG patients. CONCLUSION: These findings suggested that PD patients with FoG require additional cognitive resources to compensate their damaged automaticity in locomotor control, which is more pronounced in severe FoG patients than milder ones.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/etiologia , Postura Sentada , Marcha/fisiologia , Dedos do Pé
2.
BMC Neurol ; 22(1): 320, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008796

RESUMO

BACKGROUND: Quality of life (QoL) in patients with Parkinson's disease (PD) is increasingly used as an efficacy outcome in clinical studies of PD to evaluate the impact of treatment from the patient's perspective. Studies demonstrating the treatment effect of pramipexole on QoL remain inconclusive. This study aims to evaluate the effect of pramipexole on QoL in patients with PD by conducting a systematic review and meta-analysis of existing clinical trials. METHODS: A systematic literature search of PubMed, Embase and the Cochrane Library was performed from inception to 30 April 2022 to identify randomised, placebo-controlled trials of patients with idiopathic PD receiving pramipexole, who reported a change from baseline in their QoL as measured by the 39-item Parkinson's Disease Questionnaire (PDQ-39). Risk of bias was independently assessed by two reviewers using the Cochrane Collaboration's tool for bias assessment. RESULTS: Of 80 eligible articles screened, six trials consisting of at least 2000 patients with early or advanced PD were included. From the synthesis of all six selected trials, a significant mean change from baseline in the PDQ-39 total score of -2.49 (95% CI, -3.43 to -1.54; p < 0.0001) was observed with pramipexole compared with placebo. A trend toward improvement in QoL was consistently observed among patients who received optimal doses of pramipexole (≥ 80% of the study population on 1.5 mg dosage), regardless of disease severity (advanced versus early) or baseline QoL levels. CONCLUSION: This meta-analysis provides evidence for the potential treatment benefit of pramipexole in improving QoL in patients with PD.


Parkinson's disease is a chronic, progressive nervous system disorder with no known cure. Patients may experience a number of symptoms including stiffness, slowness, and uncontrollable muscle movements, all of which impact their quality of life. Most clinical studies in Parkinson's disease measure the effect of treatment on improving symptoms, but other aspects such as quality of life are often overlooked. It is important to include quality of life measures in clinical studies of Parkinson's disease, such as the 39-item Parkinson's disease questionnaire (PDQ-39), to understand the impact of treatment from patients' perspectives. Pramipexole is a dopamine agonist that is well-tolerated and effective at treating Parkinson's disease symptoms. However, studies examining its effect on quality of life are inconclusive. This meta-analysis of existing clinical trials therefore aimed to evaluate the effect of pramipexole on quality of life in patients with Parkinson's disease. Six trials consisting of at least 2000 patients with early or advanced Parkinson's disease receiving treatment with pramipexole were included in this meta-analysis. Analysis of these six trials found a significant improvement in PDQ-39 total score with pramipexole compared with placebo. This meta-analysis provides new evidence for the potential treatment benefit of pramipexole in improving quality of life in patients with Parkinson's disease.


Assuntos
Doença de Parkinson , Antiparkinsonianos/uso terapêutico , Humanos , Doença de Parkinson/tratamento farmacológico , Pramipexol/uso terapêutico , Qualidade de Vida , Índice de Gravidade de Doença
3.
BMC Neurol ; 22(1): 367, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138355

RESUMO

BACKGROUND: A thorough understanding of the factors that influence patient survival in Parkinson's disease (PD) will aid in prognosis prediction and provide a new direction for disease modification treatment. Currently, there are no standardized mortality ratio (SMR) data for PD patients in the northern Chinese mainland. The main focus of this study was to determine which factors in the prospectively collected baseline characteristics can affect the survival of PD patients. In addition, for the first time, we investigated the SMR of PD patients in northern China. METHODS: Between 2009 and 2012, 218 PD patients were continuously recruited from the movement disorder clinic of the First Affiliated Hospital of Dalian Medical University and followed up until death or May 31, 2021. The prespecified prognostic variables were demographics, clinical features, lifestyle factors, and drug dose prospectively collected at baseline. To determine the independent predictors of survival during follow-up, the Cox proportional hazards model was used. Kaplan-Meier analysis was applied to estimate the overall survival curve and to compare survival between layers based on statistically significant predictors. The SMR of this northern Chinese mainland PD cohort was calculated. RESULTS: After a mean follow-up of 9.58 ± 2.27 years, 50 patients (22.90%) died. Factors that could individually predict shortened survival during follow-up included older age at onset (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.06-1.15), Hoehn and Yahr (H&Y) stage ≥ 3 (HR 9.36, 95% CI 2.82-31.03) and severe cognitive impairment (HR 6.18, 95% CI 2.75-13.88). Univariate Cox regression revealed that a certain amount of physical activity was associated with better survival (HR 0.41, 95% CI 0.22-0.74), while fatigue was associated with an increased risk of death (HR 2.54, 95% CI 1.37-4.70). The overall SMR was 1.32 (95% CI 0.98-1.74). CONCLUSIONS: Older age at onset, higher baseline H&Y stage, and severe cognitive impairment have a negative impact on survival. The 10-year survival of PD patients is not significantly different from that of the general population in China.


Assuntos
Doença de Parkinson , China/epidemiologia , Estudos de Coortes , Seguimentos , Humanos , Doença de Parkinson/epidemiologia , Modelos de Riscos Proporcionais
4.
Stereotact Funct Neurosurg ; 97(2): 120-126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31288239

RESUMO

OBJECTIVES: To explore the guidance value of preoperative 3-dimensional brain volume (3D-BRAVO) and 3-dimensional time-of-flight (3D-TOF) MRA scanning for microvascular decompression. METHODS: One hundred thirteen patients treated with microvascular decompression from February 2016 to February 2018 in the First Affiliated Hospital of Dalian Medical University were retrospectively analyzed. All patients received 3D-BRAVO combined with 3D-TOF MRA sequence reconstruction before the operation. The anatomical relationship of neurovascular tissues was analyzed and compared with the results of intraoperative exploration. RESULTS: The results of MVD showed that the number of positive cases was 108 (95.6%) on the diseased side. 3D-BRAVO combined with 3D-TOF sequence reconstruction resulted in 106 positive cases (93.8%), with a 98.1% positive coincidence rate and a 13.2% false positive rate (p < 0.05). 3D-BRAVO-TOF sequence reconstruction of trigeminal neuralgia showed a positive coincidence in 78 cases (92.8%) and for hemifacial spasm a positive coincidence was found in 27 cases (93.1%). CONCLUSION: 3D-BRAVO combined with 3D-TOF sequence reconstruction before microvascular decompression can fully evaluate the morphology, location, and anatomical relationship of lesions, which is of guidance value for clinical diagnosis and treatment.


Assuntos
Imageamento Tridimensional/métodos , Angiografia por Ressonância Magnética/métodos , Cirurgia de Descompressão Microvascular/métodos , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Feminino , Espasmo Hemifacial/diagnóstico por imagem , Espasmo Hemifacial/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Neuroimmunomodulation ; 23(1): 41-57, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26468875

RESUMO

OBJECTIVES: We investigated whether Ginkgo biloba extract (EGb761) can provide neuroprotective effects and enhance the efficacy of bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model of experimental autoimmune encephalomyelitis (EAE). METHODS: We examined the synergistic action of BMSCs combined with EGb761 treatment in EAE rats. The immunized rats received an intravenous injection of BMSCs or intraperitoneal administration of EGb761 or both on the day of the onset of clinical symptoms and for the following 21 days. Clinical severity scores were recorded daily and histopathological examination of the spinal cord and cytokine concentrations in the serum were studied on days 14 and 31 postimmunization. RESULTS: Our results showed that combined treatment with BMSCs and EGb761 further decreased the disease severity, maximal clinical score and number of infiltrated mononuclear cells, especially CD3-positive T cells. We observed that the demyelination score and the density of axonal loss in the spinal cord were significantly reduced in mice receiving the combination therapy. The serum concentrations of the phosphorylated neurofilament heavy chain, tumor necrosis factor-α and interferon-γ were reduced in the combination-treatment group. CONCLUSION: Our results suggest that combined treatment with BMSCs and EGb761 have a synergistic effect in rats with EAE by inhibiting the secretion of proinflammatory cytokines, demyelination and protecting axons and neurons.


Assuntos
Encefalomielite Autoimune Experimental/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Complexo CD3/metabolismo , Movimento Celular/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/patologia , Feminino , Ginkgo biloba , Células-Tronco Mesenquimais/efeitos dos fármacos , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Coloração pela Prata , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Medula Espinal/ultraestrutura , Estatísticas não Paramétricas
6.
Eur Neurol ; 73(5-6): 337-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25997849

RESUMO

PURPOSE: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. METHODS: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families. RESULTS: The age of onset was 56.4 ± 2.7 (range, 32-76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2-120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients. CONCLUSIONS: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved.


Assuntos
Blefarospasmo/diagnóstico , Adulto , Idoso , Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , China , Diagnóstico Diferencial , Síndromes do Olho Seco/diagnóstico , Feminino , Humanos , Ceratoconjuntivite/diagnóstico , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/diagnóstico , Fármacos Neuromusculares/uso terapêutico , Estudos Retrospectivos
7.
Metab Brain Dis ; 29(1): 193-205, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24458787

RESUMO

Glutamate excitotoxicity has been implicated as one of the pathological mechanisms contributing to neuronal cell death and is involved in many neurological disorders. Stem cell transplantation is a promising approach for the treatment of nervous system damage or diseases. Previous studies have shown that mesenchymal stem cells (MSCs) have important therapeutic effects in experimental animal and preclinical disease model of central nervous system pathology. However, it is not well understood whether neurogenesis of MSCs or MSC conditioned-medium (CM) containing microparticles mediates therapeutic effects. Here, we investigated the neuroprotective effects of human adipose-derived MSCs (AMSCs) on cortical neurons using models of glutamate excitotoxicity. Following exposure to glutamate (100 µM, 15 min), cortical neurons were co-cultured with either AMSCs separated by a semiporous membrane (prohibiting direct cell-cell contact) or with AMSC-CM for 18 h. Compared to untreated control groups, AMSCs and AMSC-CM partially and similarly reduced neuronal cell damages, as indicated by reduced LDH release, a decreased number of trypan-positive cells and a decline in the number of apoptotic nuclei. Protection by CM was associated with increased GAP-43 expression and an elevated number of GAP-43-positive neurites. Furthermore, CM increased levels of ATP, NAD(+) and NADH and the ratio of NAD(+)/NADH, while preventing a glutamate-induced decline in mitochondrial membrane potential. These results demonstrate that AMSC-CM mediates direct neuroprotection by inhibiting neuronal cell damage/apoptosis, promoting nerve regeneration and repair, and restoring bioenergy following energy depletion caused by glutamate excitotoxicity.


Assuntos
Tecido Adiposo/citologia , Metabolismo Energético , Proteína GAP-43/biossíntese , Ácido Glutâmico/toxicidade , Células-Tronco Mesenquimais/metabolismo , Neurônios/metabolismo , Neurotoxinas/toxicidade , Trifosfato de Adenosina/metabolismo , Adulto , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Metabolismo Energético/efeitos dos fármacos , Proteína GAP-43/genética , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NAD/metabolismo , Neuritos/química , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
8.
J Affect Disord ; 354: 126-135, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479517

RESUMO

BACKGROUND: Emotion regulation deficits, particularly in cognitive reappraisal, are crucial in depression and anxiety. However, research on the neural mechanisms of implicit emotion regulation is lacking, and it remains unclear whether these mechanisms are shared or distinct between the two disorders. METHODS: We investigated the neural mechanisms of implicit cognitive reappraisal in 28 individuals with major depressive disorder (MDD), 25 with generalized anxiety disorder (GAD), and 30 healthy controls (HC) using functional near-infrared spectroscopy (fNIRS). Participants completed an implicit cognitive reappraisal task and underwent neuropsychological and clinical assessments. RESULTS: We found that MDD patients reported higher levels of rumination and lower utilization of cognitive reappraisal, while GAD patients reported reduced use of perspective-taking. Notably, both MDD and GAD patients exhibited decreased activation in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared to HC participants during implicit cognitive reappraisal. Specifically, inadequate OFC activation was observed in MDD patients, while GAD patients demonstrated OFC deactivation during the task. Furthermore, DLPFC activation showed a negative correlation with depression severity in MDD patients, while OFC activation was positively correlated with perspective-taking in GAD patients. LIMITATIONS: fNIRS has limited depth and spatial resolution. CONCLUSION: Our fNIRS study is the first to reveal shared and distinct neurobiological profiles of depression and anxiety in implicit emotion regulation. These findings underscore the significance of reduced DLPFC/OFC activation in emotion regulation impairment and highlight unique OFC activation patterns in these disorders. These insights have potential implications for developing cognitive-behavioral therapy and transcranial magnetic stimulation as treatment approaches.


Assuntos
Transtorno Depressivo Maior , Regulação Emocional , Humanos , Emoções/fisiologia , Transtorno Depressivo Maior/psicologia , Depressão , Imageamento por Ressonância Magnética , Transtornos de Ansiedade/psicologia , Ansiedade , Córtex Pré-Frontal/diagnóstico por imagem
9.
Trials ; 24(1): 349, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37221541

RESUMO

BACKGROUND: Night shift work-related disturbed biological rhythm and insufficient sleep affect the functioning of brain activity and thus impair cognitive performance and mood state, which potentially leads to negative and even devastating results for both individuals and patients. A virtual reality (VR)-based restorative environment has shown to be an effective new technique to reduce stress and improve cognitive performance, but little is known about its mechanism of improving neuronal activity and connectivity. METHODS: This is a randomized, controlled, single-center clinical trial. A total of 140 medical staff will be enrolled and randomized in a 1:1 allocation to either the VR immersion group (intervention group) or the control group. In the morning after the night shift, the participants in the intervention group will watch 360° panoramic videos of immersive VR natural restorative environments for 10 min, while the participants in the control group will just rest for 10 min. Assessments of abbreviated Profile of Mood States Questionnaire (POMS) and verbal fluency task (VFT) performances, as well as oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) and total hemoglobin concentration acquired by functional near-infrared spectroscopy (fNIRS) will be performed at baseline (day work), the morning after night shift but before the intervention (previous) and after intervention (post). Data collected after a night shift will be compared to baseline performance as well as between the two groups. DISCUSSION: This trial will investigate the effects of the night shift and VR-based restorative environment intervention on mood, cognitive performance, and neuronal activity and connectivity. A positive result in this trial could encourage hospitals to apply VR technology to reduce physical and mental dysfunction during of night shifts among medical staff in every department. Furthermore, the findings from this study will contribute to understanding the underlying neuromodulation mechanisms of how restorative environments influence mood and cognition. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200064769 . Registered on 17 October 2022.


Assuntos
Afeto , Corpo Clínico , Humanos , China , Oxiemoglobinas , Córtex Pré-Frontal , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Front Neurol ; 14: 1105483, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816573

RESUMO

Objective: We aimed to analyze prepulse inhibition (PPI) impairment of the blink reflex in patients with primary blepharospasm (BSP). Methods: We recruited 30 BSP patients and 20 gender- and age-matched healthy controls (HCs). Weak electrical stimulation was applied to the right index finger at interstimulus intervals (ISIs) of 120, 200, and 300 ms before the supraorbital nerve stimulation to investigate PPI size [PPI size = (1 - R2 area at prepulse trials/R2 area at baseline trials) × 100%]. Results: The prepulse stimulus significantly inhibited the R 2 component at the three ISIs in both groups, but less inhibition was shown in the BSP group (p < 0.05). In HCs, the prepulse stimulus induced prolonged R 2 and R 2c latencies at the three ISIs and increased the R 1 amplitude at ISIs of 120 ms; these changes were absent in BSP patients. In the BSP group, patients with sensory tricks showed better PPI than patients without sensory tricks. Disease duration and motor symptom severity showed no significant correlation with PPI size. Conclusion: In BSP patients, PPI was impaired while R 1 facilitation was absent. PPI size did not correlate with the motor symptom severity and disease duration. Patients with sensory tricks showed better PPI than those without sensory tricks.

12.
Front Neurol ; 14: 1273935, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020657

RESUMO

Objective: Primary blepharospasm (BSP) is a clinically heterogeneous disease that manifests not only as spasmodic closure of the eyelids but also sometimes with apraxia of eyelid opening (AEO). This cross-sectional study aimed to investigate differences in the neural mechanisms of isolated BSP and BSP-associated AEO subtypes, which may reveal the pathophysiology underlying different phenotypes. Methods: A total of 29 patients manifested as isolated BSP, 17 patients manifested as BSP associated with AEO, and 28 healthy controls underwent resting-state functional near-infrared spectroscopy (fNIRS). We assessed functional connectivity (FC) between regions of interest (ROIs) in the fronto-parietal control network (PFCN) and sensorimotor network (SMN). We also examined the relationship between altered FC and behavioral data. Results: In the FPCN, ROI- analyses showed decreased FC between the left premotor cortex and supramarginal gyrus in the BSP with AEO group compared to the isolated BSP group. In the SMN, both subgroups showed hypoconnectivity of the left premotor cortex with the right primary motor cortex, primary sensory cortex, and somatosensory association cortex. This hypoconnectivity was positively correlated with the total number of botulinum toxin A treatments, which suggests that long-term botulinum toxin A treatment may modulate motor sequence planning and coordination. Conclusion: These findings showed different connectivity alterations in neural networks associated with motor and cognitive control among different behavioral phenotypes of BSP. The identification of specific alterations in various networks that correspond to clinical heterogeneity may inform the identification of potential biomarkers for early diagnosis and personalized neuromodulation targets for treating different BSP subphenotypes.

13.
Front Aging Neurosci ; 15: 1290108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38274985

RESUMO

Purpose: Rapid eye movement sleep behavior disorder (RBD) affects 30%-40% of patients with Parkinson's disease (PD) and has been linked to a higher risk of cognitive impairment, especially executive dysfunction. The aim of this study was to investigate the brain activation patterns in PD patients with RBD (PD-RBD+) compared to those without RBD (PD-RBD-) and healthy controls (HCs), and to analyze the correlation between changes in cerebral cortex activity and the severity of RBD. Methods: We recruited 50 PD patients, including 30 PD-RBD+, 20 PD-RBD-, and 20 HCs. We used functional near infrared spectroscopy during a verbal fluency task (VFT-fNIRS) and clinical neuropsychological assessment to explore the correlation between PD-RBD+ and executive function and changes in neural activity. Results: The VFT-fNIRS analysis revealed a significant reduction in activation among PD-RBD+ patients across multiple channels when compared to both the PD-RBD- and HC groups. Specifically, PD-RBD+ patients exhibited diminished activation in the bilateral dorsolateral prefrontal cortex (DLPFC) and the right ventrolateral prefrontal cortex (VLPFC) relative to their PD-RBD- counterparts. Furthermore, compared to the HC group, PD-RBD+ patients displayed reduced activation specifically in the right DLPFC. Significantly, a noteworthy negative correlation was identified between the average change in oxygenated hemoglobin concentration (ΔHbO2) in the right DLPFC of PD-RBD+ patients and the severity of their RBD. Conclusion: Our study offers compelling evidence that RBD exacerbates cognitive impairment in PD, manifested as executive dysfunction, primarily attributed to reduced prefrontal activation. These aberrations in brain activation may potentially correlate with the severity of RBD.

14.
Drug Saf ; 46(7): 637-646, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37195560

RESUMO

INTRODUCTION: Rasagiline is indicated for treating idiopathic Parkinson's disease (PD) as monotherapy and adjunct therapy to levodopa in patients. OBJECTIVES: To assess the post-marketing safety and tolerability of rasagiline in Chinese PD patients, as well as its effectiveness in improving motor symptoms. METHODS: This prospective, non-interventional, multicenter, cohort study included PD patients administered rasagiline monotherapy or adjunct therapy to levodopa. The primary outcome was the incidence of adverse drug reactions (ADRs) according to MedDRA® (version 22.0), and the secondary outcomes were the Parkinson's Disease Unified Rating Scale (UPDRS) part III, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Global-Improvement (CGI-I), assessed at Weeks 4, 12, and 24. RESULTS: In total, 734 patients, 95 in the monotherapy subgroup and 639 in the adjunct therapy subgroup, were included in the safety population. The incidence rates of all ADRs were comparable between the monotherapy (15.8%) and adjunct therapy (13.6%) subgroups. The most common ADRs by system organ class were nervous system disorders (5.6%), gastrointestinal disorders (3.3%), psychiatric disorders (1.8%), vascular disorders (1.2%), and general disorders and administration site conditions (1.1%). Five (0.7%) participants experienced 5 serious ADRs. Improvements in UPDRS part III, CGI-S and CGI-I at Weeks 4, 12 and 24 from baseline were observed. CONCLUSIONS: Safety data in this study indicated no extra safety concerns. Rasagiline is generally safe and well tolerated in Chinese PD patients. The safety profile and tolerability were in line with the established safety profile. Moreover, rasagiline reduced the severity of PD motor symptoms, confirming findings by previous clinical trials.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Levodopa/efeitos adversos , Estudos de Coortes , População do Leste Asiático , Estudos Prospectivos , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Resultado do Tratamento
15.
Behav Brain Res ; 431: 113923, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35550840

RESUMO

Parkinson's disease (PD) is a prevailing neurodegenerative disorder. This study discussed the mechanism of lncRNA distal-less homeobox 6 antisense 1 (DLX6-AS1) on inflammatory responses in PD. With healthy male C57BL/6 mice (8-10 weeks) and BV2 microglia as study subjects, we established PD models in vivo/in vitro by injection of 1-methyl-4-phenyl-2, 3, 6-tetrahydropyridine (MPTP) for 4 weeks and treatment of lipopolysaccharide (LPS) for 24 h, respectively. DLX6-AS1 expression in PD mice and BV2 microglia was examined using reverse transcription quantitative-polymerase chain reaction and then down-regulated via stereotaxic catheter injection or cell transfection to evaluate its effect on neurological function. Meanwhile, the cell number of TH+ /Caspase3 + /IBA1 + in substantia nigra, cell viability, and apoptosis rate of BV2 microglia, inflammatory levels, and NLR family pyrin domain containing 3 (NLRP3) inflammasome were determined using immunohistochemistry, MTT assay, flow cytometry, ELIZA assay, and Western blot. The binding relationship between miR-223-3p and DLX6-AS1/Neuropilin-1 (NRP1) was verified by dual-luciferase assay and RNA immunoprecipitation assay. After down-regulation of DLX6-AS1, we down-regulated/overexpressed miR-223-3p/NRP1 levels in BV2 microglia. DLX6-AS1 was overexpressed in PD mice. Silencing DLX6-AS1 improved neurological function and alleviated microglial inflammation in PD mice. Specifically, the latency of mice falling from the rotating rod was longer, and the latency of climbing rod test was shorter; TH+ cells increased, while Caspase3 + /IBA1 + cells decreased; the levels of inflammatory were lowered. Silencing DLX6-AS1 inhibited LPS-induced inflammation of BV2 microglia. DLX6-AS1 acted as the ceRNA of miR-223-3p to promote NRP1. Down-regulation of miR-223-3p or overexpression of NRP1 partially annulled the effect of silencing DLX6-AS1 on BV2 microglial inflammation. Overall, DLX6-AS1 promotes the microglial inflammatory response in PD through the ceRNA mechanism of miR-223-3p/NRP1.


Assuntos
MicroRNAs , Doença de Parkinson , RNA Longo não Codificante , Animais , Proteínas de Homeodomínio/genética , Humanos , Inflamação/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Microglia/metabolismo , Neuropilina-1/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , RNA Longo não Codificante/genética
16.
Eur J Med Res ; 27(1): 38, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35272706

RESUMO

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder characterized by complex neuropsychiatric syndromes during disease onset. Although this disease has been well documented in the last decade, clinical characteristics of anti-NMDA receptor encephalitis in patients with long-term diagnostic history of mental disorders remain unclear. METHODS: Here, we reviewed and analyzed series of anti-NMDA receptor encephalitis patients with a long-term medical history of psychiatric disorders through a review of literature using PubMed, web of science and Embase database. In addition, we described a patient of anti-NMDA receptor encephalitis with a long-term history of major depressive disorder. RESULTS: A total of 14 patients with anti-NMDA receptor encephalitis and a long-term history of mental disorders were included in our study. We found that most patients were adult (92.9%) and female (78.6%). These patients often first visited a psychiatric department (71.43%). The mean disease course of psychiatric disorders was more than 9 years. Speech impairment (71.4%), abnormal behaviors (64.3%), and catatonia (64.3%) were the most common clinical symptoms. Most patients (85.7%) had a satisfactory prognosis after immunotherapy. CONCLUSION: Anti-NMDA receptor encephalitis in individuals with mental disorders is an underestimated condition, yet it presents complex clinical symptoms. Mental and behavioral impairments are more frequently observed in newly diagnosed anti-NMDA receptor encephalitis patients with a long-term history of mental disorders than those without mental illness. A diagnosis of anti-NMDA receptor encephalitis should be considered when patients with mental illness show sudden fluctuations in psychiatric symptoms.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Imunoterapia/métodos , Transtornos Mentais/complicações , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Seguimentos , Humanos , Masculino , Fatores de Tempo
17.
Parkinsonism Relat Disord ; 105: 96-102, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36401901

RESUMO

INTRODUCTION: The use of the anti-parkinsonian drug trihexyphenidyl (THP) to treat patients with Parkinson's disease (PD), particularly those with tremor-dominant PD (tdPD), has been well documented. Despite growing concerns about THP causing cognitive decline in tdPD patients, the underlying neural correlates remain unclear. Therefore, we investigated the effects of THP on prefrontal executive function and spontaneous neural activity in patients with tdPD by utilizing functional near-infrared spectroscopy (fNIRS). METHODS: We recruited 30 patients with tdPD, including 15 patients receiving THP and 15 patients not receiving THP. We performed comprehensive neuropsychological and clinical assessments to evaluate each patient's cognitive function, mental status, and clinical symptoms. We measured brain activation elicited from the verbal fluency task (VFT) and changes in amplitude of low-frequency fluctuations (ALFF) at rest to investigate executive function and spontaneous neural activity, respectively. In addition, we examined the relationship between altered activation during task and resting state and neuropsychological and clinical data. RESULTS: Compared with tdPD patients not taking THP, tdPD patients taking THP showed no differences on neuropsychological tests. However, there was insufficient activity of the dorsolateral prefrontal cortex (DLPFC) during VFT and reduced ALFF values for the DLPFC, ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC) related to the frontoparietal network (FPN) at rest. Furthermore, ALFF values of the VLPFC were positively correlated with scores of multiple cognitive domain functions. CONCLUSION: These findings suggest that THP treatment may lead to prefrontal dysfunction in tdPD patients, attenuating brain activation in executive function and cognition-related spontaneous neural activity.


Assuntos
Doença de Parkinson , Tremor , Humanos , Tremor/diagnóstico por imagem , Tremor/tratamento farmacológico , Tremor/etiologia , Triexifenidil , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Função Executiva , Cognição
18.
Int J Neural Syst ; 32(2): 2150048, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34635034

RESUMO

Seizure prediction using intracranial electroencephalogram (iEEG) has attracted an increasing attention during recent years. iEEG signals are commonly recorded in the form of multiple channels. Many previous studies generally used the iEEG signals of all channels to predict seizures, ignoring the consideration of channel selection. In this study, a method of one-dimensional convolutional neural networks (1D-CNN) combined with channel selection strategy was proposed for seizure prediction. First, we used 30-s sliding windows to segment the raw iEEG signals. Then, the 30-s iEEG segments, which were in three channel forms (single channel, channels only from seizure onset or free zone and all channels from seizure onset and free zones), were used as the inputs of 1D-CNN for classification, and the patient-specific model was trained. Finally, the channel form with the best classification was selected for each patient. The proposed method was evaluated on the Freiburg Hospital iEEG dataset. In the situation of seizure occurrence period (SOP) of 30[Formula: see text]min and seizure prediction horizon (SPH) of 5[Formula: see text]min, 98.60[Formula: see text] accuracy, 98.85[Formula: see text] sensitivity and 0.01/h false prediction rate (FPR) were achieved. In the situation of SOP of 60[Formula: see text]min and SPH of 5[Formula: see text]min, 98.32[Formula: see text] accuracy, 98.48[Formula: see text] sensitivity and 0.01/h FPR were attained. Compared with the many existing methods using the same iEEG dataset, our method showed a better performance.


Assuntos
Eletrocorticografia , Convulsões , Eletroencefalografia , Humanos , Redes Neurais de Computação , Convulsões/diagnóstico
19.
Front Psychiatry ; 13: 960953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159948

RESUMO

Informal Parkinson's disease (PD) caregivers are considered to experience high levels of caregiver burden, negatively affecting the health of caregivers. However, few studies explored the relationship between anxiety in caregiver burden and cognitive function in informal PD caregivers. Although, no study has even investigated the neural mechanisms underlying this connection. This study aimed to conduct comprehensive cognitive and clinical assessments and evaluate brain activity from task-based state and resting-state using functional near-infrared spectroscopy (fNIRS). A total of ten informal PD caregivers and 15 matched, healthy, non-caregivers were recruited. Comprehensive cognitive and clinical assessments were conducted to evaluate five cognitive domains and mental states. Neural activity induced by verbal fluency task (VFT) and brain connectivity during resting state were monitored, and their correlations with the neuropsychological and clinical tests were explored. Our results showed that compared to non-caregiver, an informal PD caregiver exhibited no difference in most cognitive domains of function but performed better in attentional function, along with higher levels of anxiety. Decreased activation over prefrontal regions during VFT and hypo-connectivity within the frontoparietal network (FPN) and between default mode network (DMN) and FPN in the resting state were confirmed in this study as a result of the negative effects of anxiety on the brain. Furthermore, Spearman's correlation found that neural activity in FPN during task-based state and resting state was negatively correlated with the severity of anxiety. These findings indicate that despite normal or even better cognitive function, informal PD caregivers have impaired brain function, and this deficit in neural activity was related to anxiety.

20.
Eur J Med Res ; 26(1): 138, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876223

RESUMO

BACKGROUND:  Hemifacial spasm (HFS) is a movement disorder caused by mechanical compression of the facial nerve after it has left the brainstem and is characterized by brief or sustained twitching of the muscles innervated by that nerve. Often we observe spasm in an awakening situation. Actually contractions persist during sleep. To our knowledge, there were no reports on how HFS manifests under disturbance of consciousness. Here, we report a case of primary HFS in which the patient's symptoms persisted in a coma. CASE PRESENTATION: A 74-year-old female with right-sided primary HFS for 20 years and had received botulinum toxin injections in our hospital. Unfortunately she was carried to emergency department after traumatic right pneumothorax by accident. During the emergency treatment, she lost consciousness due to simultaneous cardiac arrest and respiratory arrest. She was then admitted to the emergency intensive care unit for further treatment. During her hospitalization, she was in a coma with stable vital signs and persisting symptoms of HFS. Thus, a multidisciplinary consultation was requested to identify whether it was focal cortical seizures involving the right-side facial muscles. Physical examination revealed brief involuntary clonic or tonic contractions accompanied with the 'Babinski-2 sign'. A combination of relevant data, including her past history, clinical presentation and a negative computed tomography scan of the head, led to a diagnosis of right-sided HFS. As the symptoms of HFS are not life-threatening, the use of anticonvulsants is unnecessary. CONCLUSIONS: For the layperson, it is crucial to seek a multidisciplinary consultation to obtain a correct diagnosis.


Assuntos
Estado de Consciência/fisiologia , Nervo Facial/fisiopatologia , Espasmo Hemifacial/etiologia , Idoso , Feminino , Espasmo Hemifacial/fisiopatologia , Humanos , Polissonografia , Tomografia Computadorizada por Raios X
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