Pei-Chin Chen

White matter damage and systemic inflammation in obstructive sleep apnea.

STUDY OBJECTIVES To evaluate white matter integrity in patients with obstructive sleep apnea (OSA) using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation. DESIGN Cross-sectional study. SETTING One tertiary medical center research institute. PATIENTS OR PARTICIPANTS Twenty patients with severe OSA (apnea-hypopnea index [AHI] > 30, 18 men and 2 women) and 14 healthy volunteers (AHI < 5, 11 men and 3 women). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Patients with severe OSA and healthy volunteers underwent polysomnography to determine the severity of sleep apnea, and DTI scanning to determine fiber integrity. Early or late phase changes in leukocyte apoptosis and its subsets were determined by flow cytometry. DTI-related indices (including fractional anisotropy [FA], axial diffusivity [AD], radial diffusivity [RD], and mean diffusivity [MD]) were derived from DTI. The FA maps were compared using voxel-based statistics to determine differences between the severe OSA and control groups. The differences in DTI indices, clinical severity, and leukocyte apoptosis were correlated after adjusting for age, sex, body mass index, and systolic blood pressure. Exploratory group-wise comparison between the two groups revealed that patients with OSA exhibited low FA accomplished by high RD in several brain locations, without any differences in AD and MD. The FA values were negatively correlated with clinical disease severity and leukocyte early apoptosis. CONCLUSIONS Obstructive sleep apnea impairs white matter integrity in vulnerable regions, and this impairment is associated with increased disease severity. The possible interactions between systemic inflammation and central nervous system microstructural damage may represent variant hypoxic patterns and their consequent processes in OSA.

Structural covariance networks of striatum subdivision in patients with Parkinson's disease

Parkinsons disease (PD) is a neurodegenerative disorder associated with the striatum. Previous studies indicated that subdivisions of the striatum with distinct functional connectivity profiles contribute to different pathogeneses in PD. Segregated structural covariance (SC) pattern between the striatum and neocortex observed in healthy subjects, however, remain unknown in PD. The purpose of this study is to map and compare the subregional striatal SC network organization between 30 healthy controls and 48 PD patients and to investigate their association with the disease severity. The striatal SC network was statistically inferred by correlating the mean gray matter (GM) volume of six striatal subdivisions (including the bilateral dorsal caudate, superior ventral striatum, inferior ventral striatum, dorsal caudal putamen, dorsal rostral putamen, and ventral rostral putamen) with the entire neocortical GM volume in voxel‐wise manner. The PD patients revealed marked atrophy in the striatum, cerebellum, and extra‐striatum neocortices. As predicted, segregated striatal SC network patterns were observed in both groups. This suggests that in PD, pathological processes occurring in the striatum affect the same striato‐cortical networks that covary with the striatum in healthy brains. The PD patients further demonstrated atypical striatal SC patterns between the caudate, parahippocampus temporal cortices, and cerebellum, which corresponded to dopaminergic associated network. The areas with significant group differences in SC were further associated with disease severity. Our findings support previous studies indicating that PD is associated with altered striato‐cortical networks, and suggest that structural changes in the striatum may result in a cascade of alterations in multiple neocortices. Hum Brain Mapp 36:1567–1584, 2015.

Structural and cognitive deficits in chronic carbon monoxide intoxication: a voxel-based morphometry study

BackgroundPatients with carbon monoxide (CO) intoxication may develop ongoing neurological and psychiatric symptoms that ebb and flow, a condition often called delayed encephalopathy (DE). The association between morphologic changes in the brain and neuropsychological deficits in DE is poorly understood.MethodsMagnetic resonance imaging and neuropsychological tests were conducted on 11 CO patients with DE, 11 patients without DE, and 15 age-, sex-, and education-matched healthy subjects. Differences in gray matter volume (GMV) between the subgroups were assessed and further correlated with diminished cognitive functioning.ResultsAs a group, the patients had lower regional GMV compared to controls in the following regions: basal ganglia, left claustrum, right amygdala, left hippocampus, parietal lobes, and left frontal lobe. The reduced GMV in the bilateral basal ganglia, left post-central gyrus, and left hippocampus correlated with decreased perceptual organization and processing speed function. Those CO patients characterized by DE patients had a lower GMV in the left anterior cingulate and right amygdala, as well as lower levels of cognitive function, than the non-DE patients.ConclusionsPatients with CO intoxication in the chronic stage showed a worse cognitive and morphologic outcome, especially those with DE. This study provides additional evidence of gray matter structural abnormalities in the pathophysiology of DE in chronic CO intoxicated patients.

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.

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.

Diffusion tensor imaging study of white matter damage in chronic meningitis.

Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation.

Systemic inflammation and alterations to cerebral blood flow in obstructive sleep apnea

Systemic inflammation and alterations to regional cerebral blood flow (CBF) have been reported previously in obstructive sleep apnea (OSA). This study utilized arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI) to evaluate CBF in OSA patients and determine its relationship with systemic inflammation. Twenty male patients with moderate and severe OSA [apnea–hypopnea index (AHI) >15] and 16 healthy male volunteers (AHI <5) were recruited. Early‐ or late‐phase changes in leucocyte apoptosis and its subsets were determined by flow cytometry. Perfusion MRI data were acquired with a pulsed continuous ASL technique. The CBF maps were compared using voxel‐based statistics to determine differences between the OSA and control groups. The differences in CBF, clinical severity and leucocyte apoptosis were correlated. Exploratory groupwise comparison between the two groups revealed that the OSA patients exhibited low CBF values in the vulnerable regions. The lower regional CBF values were correlated with higher clinical disease severity and leucocyte apoptosis. OSA impairs cerebral perfusion in vulnerable regions, and this deficit is associated with increased disease severity. The apparent correlation between systemic inflammation and cerebral perfusion may be indicative of haemodynamic alterations and their consequences in OSA.

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.