Meng-Hsiang Chen

Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging.

Abstract Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning.

Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury

The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.

Peripheral Leukocyte Apoptosis in Patients with Parkinsonism: Correlation with Clinical Characteristics and Neuroimaging Findings

Apoptosis of both brain neurons and peripheral blood leukocyte is believed to be an important biomarker for evaluating the functional status of Parkinsons disease (PD). However, their correlation remains unknown. A better understanding of the pathophysiology of neurodegeneration is essential for the treatment and prevention of PD. The present study demonstrated that leukocyte apoptosis is significantly higher in PD patients and is associated with central dopamine neuron loss by using 99mTc-TRODAT-1 SPECT. The leukocyte apoptosis and striatal dopamine transporter uptake ratios were further associated with increased severity and longer duration of disease. The interaction between brain and systemic inflammation may be responsible for the neurodegenerative disease progression.

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease

AbstractPatients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD.Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex.Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation.In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD.

Associations among Cognitive Functions, Plasma DNA, and White Matter Integrity in Patients with Early-Onset Parkinson's Disease

Early-onset Parkinsons disease (EOPD) patients are symptomatic at a relatively young age, and the impacts of the disease on both the patients and their caregivers are dramatic. Few studies have reported on the cognitive impairments seen in EOPD, and the results of these studies have been diverse. Furthermore, it is still unclear what microstructural white matter (WM) changes are present in EOPD patients. As such, we conducted this study to investigate the microstructural WM changes experienced by EOPD patients and their association with cognitive function and plasma DNA levels. We enrolled 24 EOPD patients and 33 sex- and age-matched healthy volunteers who underwent complete neuro-psychological testing (NPT) to evaluate their cognitive function and diffusion tensor imaging (DTI) scanning to determine their fiber integrity. The plasma DNA measurements included measurements of nuclear and mitochondrial DNA levels. Fractional anisotropy (FA) maps were compared using voxel-based statistics to determine differences between the two groups. The differences in DTI indices and NPT scores were correlated after adjusting for age, sex, and education. Our results demonstrate that patients with EOPD have elevated nuclear DNA levels and wide spectrums of impairments in NPT, especially in the executive function and visuospatial function domains. Exploratory group-wise comparisons of the DTI indices revealed that the patients with EOPD exhibited lower DTI parameters in several brain locations. These poorer DTI parameters were associated with worse cognitive performances and elevated plasma nuclear DNA levels, especially in the anterior thalamic radiation region. Our findings suggest that the thalamus and its adjacent anterior thalamic radiation may be important in the pathogenesis of EOPD, as they appear to become involved in the disease process at an early stage.

White matter damage and systemic inflammation in Parkinson’s disease

BackgroundSystemic inflammation and white matter (WM) alterations have been noted as effects of Parkinson’s disease (PD). This study sought to evaluate WM integrity in PD patients using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation.MethodsSixty-six patients with PD (23 men and 43 women) and 67 healthy volunteers (29 men and 38 women) underwent blood sampling to quantify inflammatory markers and DTI scans to determine fiber integrity. The inflammatory markers included leukocyte apoptosis, as well as cellular and serum adhesion molecules, in each peripheral blood sample. DTI-related indices [including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] were derived from DTI scans. The resulting FA maps were compared using voxel-based statistics to determine differences between the PD and control groups. The differences in the DTI indices, clinical severity, and inflammatory markers were correlated.ResultsExploratory group-wise comparison between the two groups revealed that the PD patients exhibited extensive DTI index differences. Low FA accompanied by high RD and MD, without significant differences in AD, suggesting a demyelination process, were found in the parietal, occipital, cerebellar, and insular WM of the PD patients. The declined DTI indices were significantly correlated with increased clinical disease severity, adhesion molecules, and leukocyte apoptosis.ConclusionsPatients with PD experience WM integrity damage in vulnerable regions, and these impairments are associated with increased disease severity and systemic inflammation. The possible interactions among them may represent variant neuronal injuries and their consequent processes in PD.

Altered Striatocerebellar Metabolism and Systemic Inflammation in Parkinson’s Disease

Parkinsons disease (PD) is the most second common neurodegenerative movement disorder. Neuroinflammation due to systemic inflammation and elevated oxidative stress is considered a major factor promoting the pathogenesis of PD, but the relationship of structural brain imaging parameters to clinical inflammatory markers has not been well studied. Our aim was to evaluate the association of magnetic resonance spectroscopy (MRS) measures with inflammatory markers. Blood samples were collected from 33 patients with newly diagnosed PD and 30 healthy volunteers. MRS data including levels of N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) were measured in the bilateral basal ganglia and cerebellum. Inflammatory markers included plasma nuclear DNA, plasma mitochondrial DNA, and apoptotic leukocyte levels. The Cho/Cre ratio in the dominant basal ganglion, the dominant basal ganglia to cerebellum ratios of two MRS parameters NAA/Cre and Cho/Cre, and levels of nuclear DNA, mitochondrial DNA, and apoptotic leukocytes were significantly different between PD patients and normal healthy volunteers. Significant positive correlations were noted between MRS measures and inflammatory marker levels. In conclusion, patients with PD seem to have abnormal levels of inflammatory markers in the peripheral circulation and deficits in MRS measures in the dominant basal ganglion and cerebellum.

Plasma DNA Mediate Autonomic Dysfunctions and White Matter Injuries in Patients with Parkinson’s Disease

Background. Cardiovascular autonomic dysfunction is well known in Parkinsons disease (PD) presentation and it produces hypoperfusion of vital organs. The association between cardiovascular autonomic dysfunction and oxidative stress was examined in previous animal models. Oxidative stress and neuroinflammation were thought to have roles in PD pathogenesis. Owing to the relative low intrinsic antioxidative properties, brain white matter (WM) is vulnerable to the oxidative stress. This study is conducted to examine possible relationships by using a hypothesis-driven mediation model. Methods. Twenty-nine patients with PD and 26 healthy controls participated in this study, with complete examinations of cardiac autonomic parameters, plasma DNA level, and WM integrity. A single-level three-variable mediation model was used to investigate the possible relationships. Results. The elevated serum oxidative stress biomarkers include plasma nuclear DNA and mitochondrial DNA, and poorer cardiac autonomic parameters and multiple regional microstructural WM changes are demonstrated. Further mediation analysis shows that plasma nuclear DNA served as the mediators between poorer baroreflex sensitivity and mean diffusivity changes in cingulum. Conclusions. These results provide a possible pathophysiology for how the poor baroreflex sensitivity and higher oxidative stress adversely impacted the WM integrity. This model could provide us with a piece of the puzzle of the entire PD pathogenesis.

Autonomic Function Impairment and Brain Perfusion Deficit in Parkinson’s Disease

Introduction Autonomic disorders have been recognized as important Parkinson’s disease (PD) components. Some vulnerable structures are related to the central autonomic network and have also been linked to autonomic function alterations. The aims of the study are to evaluate the severity of the autonomic dysfunction and the cortical hypoperfusion using arterial spin labeling (ASL) MRI. And then, possible relationships of significant between-group differences in perfusion pattern to clinical variables and autonomic functions were examined to determine the pharmaceutical effects of dopaminergic treatment on cerebral blood flow (CBF) in patients with PD. Methods Brain ASL MRI was carried out in 20 patients with PD (6 men and 14 women, mean age: 63.3 ± 6.4 years) and 22 sex- and age-matched healthy volunteers to assess whole-brain CBF and the effects of dopaminergic therapy on perfusion. All subjects underwent a standardized evaluation of cardiovagal and adrenergic function including a deep breathing, Valsalva maneuver, and 5-min head-up tilt test. Perfusion MRI data were acquired on a 3.0 T scanner with a pulsed continuous ASL technique. The CBF, autonomic parameters, and clinical data were analyzed after adjusting for age and sex. Results Patients exhibited a decline in autonomic function (rapid heart rate in response to deep breathing, low baroreflex sensitivity, high systolic and diastolic pressure, and altered tilting test response), widespread low CBF, and robust response to dopaminergic therapy. Lower perfusion in the middle frontal gyrus was associated with increased clinical disease severity (Unified Parkinson’s Disease Rating Scale I score, P < 0.001). Lower perfusion in autonomic control areas, such as the frontal lobe and insula, were significantly associated with autonomic impairment (P < 0.001). Conclusions Our study indicates that PD is a progressive neurodegenerative disorder that changes the perfusion of central nervous system and is associated with variable autonomic dysfunctions. Neuronal loss and sympathetic activation may explain the interaction between cortical autonomic region perfusion and cardiovascular autonomic function.

Callosal damage and cognitive deficits in chronic carbon monoxide intoxication: A diffusion tensor imaging study

PURPOSE To evaluate the correlation between microstructural damage in the corpus callosum (CC) and the cognitive performance of patients with or without delayed encephalopathy (DE) after carbon monoxide (CO) intoxication in the chronic stage. METHODS Diffusion tensor imaging (DTI) was performed more than 6 months after CO intoxication for 10 patients with DE and 10 patients without DE recruited from out-patient clinics, as well as for 15 normal controls (NCs). Using a probabilistic tractography method to parcel the CC based on fiber projections to cortical connectivity patterns, the DTI indices were calculated in the CC subregions and further correlated with cognitive performance. RESULTS The DE group exhibited significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) values in the prefrontal, premotor, primary motor, primary sensory, parietal, and occipital CC subregions than did the NCs. The DE group also exhibited significantly lower FA values in the prefrontal and premotor subregions than did the non-DE group. Lower FA and higher RD values in the CC subregions were associated with poorer scores on the symbol search test. CONCLUSIONS CO intoxication may cause lower FA and higher RD in the CC subregions, with subsequent cognitive impairment. This finding suggests that selective CC damage after CO intoxication is more profound in patients with DE.