RESUMEN
AIMS: Fatigue is a common burdensome problem in patients with Parkinson's disease (PD), but its pathophysiological mechanisms are poorly understood. This study aimed at investigating the neural substrates of fatigue in patients with PD. METHODS: A total of 17 PD patients with fatigue, 32 PD patients without fatigue, and 25 matched healthy controls were recruited. The 9-item fatigue severity scale (FSS) was used for fatigue screening and severity rating. Resting-state functional magnetic resonance imaging (RS-fMRI) data were obtained from all subjects. Amplitude of low-frequency fluctuations (ALFF) was used to measure regional brain activity, and functional connectivity (FC) was applied to investigate functional connectivity at a network level. RESULTS: PD-related fatigue was associated with ALFF changes in right middle frontal gyrus within the attention network and in left insula as well as right midcingulate cortex within the salience network. FC analysis revealed that above three regions showing ALFF differences had altered functional connectivity mainly in the temporal, parietal, and motor cortices. CONCLUSION: Our findings do reveal that abnormal regional brain activity within attention and salience network and altered FC of above abnormal regions are involved in neural mechanism of fatigue in patients with PD.
Asunto(s)
Mapeo Encefálico , Encéfalo/fisiopatología , Fatiga/etiología , Vías Nerviosas/fisiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/patología , Descanso , Anciano , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Oxígeno/sangre , Enfermedad de Parkinson/diagnóstico por imagen , Índice de Severidad de la EnfermedadRESUMEN
AIMS: The aim of this study is to further uncover the neural basis of postural instability gait disorder (PIGD) subtype of Parkinson's disease. METHODS: With F-18 fluorodeoxyglucose PET (FDG-PET), brain glucose metabolism of patients with PIGD (n = 15) was compared with healthy controls (n = 17) and tremor-dominant (TD) patients (n = 15), and the correlation between metabolism and PIGD symptoms was also assessed. Within PIGD symptom-correlated hypometabolic areas, the relationship of functional connectivity (FC) with motor and cognitive symptoms was examined by using functional MRI. RESULTS: Compared with controls, patients with PIGD displayed a distributed pattern of brain hypometabolism including striatal, frontal, and parietal areas. Relative to the pattern of TD patients, the pattern of patients with PIGD had additional metabolic decreases in caudate and inferior parietal lobule (IPL, Brodmann area [BA] 40). In PIGD group, the metabolic reductions in IPL (BA 40), middle frontal gyrus (MFG, BA 9) and fusiform gyrus (FG, BA 20) were associated with severe PIGD symptoms. Regions showing such correlation were chosen for further seed-based FC analysis. Decreased FC within the prefrontal-parietal network (between the MFG and IPL) was associated with severe PIGD symptoms. CONCLUSION: The involvement of the caudate, FG, and prefrontal-parietal network may be associated with the prominent gait impairments of PIGD subtype. Our findings expand the pathophysiological knowledge of PIGD subtype and provide valuable information for potential neuromodulation therapies alleviating gait disorders.
Asunto(s)
Trastornos Neurológicos de la Marcha/diagnóstico por imagen , Trastornos Neurológicos de la Marcha/etiología , Imagen por Resonancia Magnética , Enfermedad de Parkinson/complicaciones , Tomografía de Emisión de Positrones , Equilibrio Postural/fisiología , Anciano , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Oxígeno , Enfermedad de Parkinson/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Temblor/diagnóstico por imagen , Temblor/etiologíaRESUMEN
Anxiety disorders in patients with Parkinson's disease (PD) are often missed due to an overlap with other non-motor symptoms. The relationships between anxiety and other non-motor symptoms in PD still remain unclear. We used the Hamilton anxiety rating scale and the Non-motor Symptoms Questionnaire to measure anxiety and the complex range of non-motor symptoms in 99 PD patients. The relationships between anxiety and other PD-related non-motor symptoms were examined through regression analyses. 25 % of PD patients were diagnosed with clinically relevant anxiety. Non-motor symptoms were more prominent in patients with anxiety. Depression, urinary disorders, and sleep disruption were the factors most likely to influence anxiety in PD. Our findings have revealed a strong interplay between anxiety and other non-motor symptoms of PD and have highlighted the need for a holistic approach towards the clinical treatment of this disabling condition.
Asunto(s)
Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/fisiopatología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Antiparkinsonianos/uso terapéutico , Trastornos de Ansiedad/complicaciones , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Escalas de Valoración Psiquiátrica , Índice de Severidad de la EnfermedadRESUMEN
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified human coronavirus. The extremely high homology of the viral genomic sequences between the viruses isolated from human (huSARS-CoV) and those of palm civet origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was subjected to the strongest positive selection pressure during transmission, and there were six amino acid residues within the receptor-binding domain of the S protein being potentially important for SARS progression and tropism. Using the single-round infection assay, we found that a two-amino acid substitution (N479K/T487S) of a huSARS-CoV for those of pcSARS-CoV almost abolished its infection of human cells expressing the SARS-CoV receptor ACE2 but no effect upon the infection of mouse ACE2 cells. Although single substitution of these two residues had no effects on the infectivity of huSARS-CoV, these recombinant S proteins bound to human ACE2 with different levels of reduced affinity, and the two-amino acid-substituted S protein showed extremely low affinity. On the contrary, substitution of these two amino acid residues of pcSARS-CoV for those of huSRAS-CoV made pcSARS-CoV capable of infecting human ACE2-expressing cells. These results suggest that amino acid residues at position 479 and 487 of the S protein are important determinants for SARS-CoV tropism and animal-to-human transmission.