Putamen Of Patients Research Articles

Parkinson's disease and Parkinsonism syndromes: Evaluating iron deposition in the putamen using magnetic susceptibility MRI techniques - A systematic review and literature analysis

Magnetic resonance imaging (MRI) techniques, such as quantitative susceptibility mapping (QSM) and susceptibility-weighted imaging (SWI), can detect iron deposition in the brain. Iron accumulation in the putamen (PUT) can contribute to the pathogenesis of Parkinson's disease (PD) and atypical Parkinsonian disorders. This systematic review aimed to synthesize evidence on iron deposition in the PUT assessed by MRI susceptibility techniques in PD and Parkinsonism syndromes. The PubMed and Scopus databases were searched for relevant studies. Thirty-four studies from January 2007 to October 2023 that used QSM, SWI, or other MRI susceptibility methods to measure putaminal iron in PD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and healthy controls (HCs) were included. Most studies have found increased putaminal iron levels in PD patients versus HCs based on higher quantitative susceptibility. Putaminal iron accumulation correlates with worse motor scores and cognitive decline in patients with PD. Evidence regarding differences in susceptibility between PD and atypical Parkinsonism is emerging, with several studies showing greater putaminal iron deposition in PSP and MSA than in PD patients. Alterations in putaminal iron levels help to distinguish these disorders from PD. Increased putaminal iron levels appear to be associated with increased disease severity and progression. Thus, magnetic susceptibility MRI techniques can detect abnormal iron accumulation in the PUT of patients with Parkinsonism. Moreover, quantifying putaminal susceptibility may serve as an MRI biomarker to monitor motor and cognitive changes in PD and aid in the differential diagnosis of Parkinsonian disorders.

Quantitative susceptibility mapping (QSM) in deep gray matter as a neurodegeneration marker in relapsing-remitting and secondary-progressive multiple sclerosis

Purpose. The aim of the study was to investigate changes in iron distribution in the brain of patients with multiple sclerosis (MS) using magnetic resonance imaging (MRI) technique – quantitative susceptibility mapping (QSM) – in comparison with clinical data.Materials and methods. Three groups of patients were included in this prospective study: 47 patients with relapsing-remitting MS (RRMS), 20 patients with secondary progressive MS (SPMS) and 39 healthy controls. For all patients we collected clinical data, including history of present illness (H&P) and disability degree, and performed brain MRI followed by QSM maps obtaining and assessing relative magnetic susceptibility in subcortical structures.Results. We found an increase in magnetic susceptibility in the heads of the caudate nuclei and in putamen in patients with SPMS as compared to RRMS. At the same time, a decrease in magnetic susceptibility in the thalamic pulvinar was detected in patients with MS in the long term, but a sharp hyperintensity in conjunction with decreasing volume was observed in some patients.Conclusion. Increased magnetic susceptibility on the QSM in subcortical structures of the brain, reflecting iron content, is more typical for patients with SPMS, which may indicate the prognostic value of these changes.

Basal Ganglia Atrophy as a Marker for Prodromal X-Linked Dystonia-Parkinsonism.

In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease-modifying therapies. X-linked dystonia-parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult-onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long-lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X-linked dystonia-parkinsonism, structural and iron-sensitive magnetic resonance imaging (MRI) was performed in 10 non-manifesting carriers and 24 healthy controls in a double-blind fashion. Seventeen patients with X-linked dystonia-parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non-manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single-nucleotide polymorphisms associated with age at onset. Voxel-based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non-manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non-manifesting carriers. Susceptibility-weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non-manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X-linked dystonia-parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X-linked dystonia-parkinsonism. ANN NEUROL 2023;93:999-1011.

Association between susceptibility value and cerebral blood flow in the bilateral putamen in patients undergoing hemodialysis

Hemodialysis (HD) is the most regularly applied replacement therapy for end-stage renal disease, but it may result in brain injuries. The correlation between cerebral blood flow (CBF) alteration and iron deposition has not been investigated in patients undergoing HD. Ferritin level may be a dominant factor in CBF and iron deposition change. We hypothesize that ferritin level might be the key mediator between iron deposition and CBF alteration. The correlation in the putamen was estimated between the susceptibility values and CBF in patients undergoing HD. Compared with healthy controls, patients showed more altered global susceptibility values and CBF. The susceptibility value was negatively correlated with CBF in the putamen in patients. Moreover, the susceptibility value was negatively correlated with ferritin level and positively correlated with serum iron level in the putamen of patients. CBF was positively correlated with ferritin level and negatively correlated with serum iron level in the putamen of patients. These findings indicate that iron dyshomeostasis and vascular damage might exist in the putamen in patients. The results revealed that iron dyshomeostasis and vascular damage in the putamen may be potential neural mechanisms for neurodegenerative processes in patients undergoing HD.

Cerebral blood flow is associated with markers of neurodegeneration in Huntington’s disease

IntroductionThe ultimate cause of neuronal death in Huntington's disease (HD) is still uncertain. Apart from impairment in systems handling abnormal proteins, other mechanisms might contribute to neurodegeneration and progression of HD. Decreased cerebral blood flow (CBF) has been described in other neurodegenerative disorders and may play a role in HD. ObjectivesTo investigate CBF changes in HD gene carriers. MethodsA group of 39 HD gene carriers (18 premanifest and 21 manifest HD) and 16 controls underwent a comprehensive clinical evaluation and a brain magnetic resonance imaging protocol that included pseudo-continuous arterial spin labeling to quantify CBF. Regions of interest (ROI) analyses were performed to compare CBF in controls vs premanifest HD vs manifest HD. Correlation analyses were performed to ascertain the relationship between CBF and clinical and biomarkers data. ResultsWe found a decrease in CBF in bilateral caudate and putamen of patients with manifest HD in comparison with controls. CBF of premanifest HD carriers in the same ROIs was midway between controls and the HD patients, with differences not reaching statistical significance. Lower CBF in caudate and putamen was associated with worse motor symptoms, functionality, and cognitive performance. CBF was also associated with markers of neurodegeneration: higher CBF in caudate and putamen significantly correlated to higher volumes in the same ROI and to lower levels of neurofilament light chain. ConclusionAs CBF changes in caudate and putamen nuclei were associated with markers of neurodegeneration and with clinical outcomes, decreased CBF and oxygen supply could emerge as a relevant mechanism contributing to degeneration in HD.

Involvement of autophagic protein DEF8 in Lewy bodies

Dysregulation of autophagy, one of the major processes through which abnormal proteins are degraded, is a cardinal feature of synucleinopathies, including Lewy body diseases [Parkinson's disease (PD) and dementia with Lewy bodies (DLB)] and multiple system atrophy (MSA), which are characterized by the presence of abnormal α-synuclein in neurons and glial cells. Although several research groups have reported that Rubicon family proteins can regulate autophagosome-lysosome fusion or positioning, little is known about their involvement in synucleinopathies. In the present study, by studying patients with PD (N = 8), DLB (N = 13), and MSA (N = 5) and controls (N = 16), we explored the involvement of Rubicon family proteins [Rubicon, Pacer and differentially expressed in FDCP8 (DEF8)] in synucleinopathies. Immunohistochemical analysis showed that not only brainstem-type Lewy bodies but also cortical Lewy bodies were immunoreactive for DEF8 in Lewy body diseases, whereas Rubicon and Pacer were detectable in only a few brainstem-type Lewy bodies in PD. Glial cytoplasmic inclusions in patients with MSA were not immunoreactive for Rubicon, Pacer or DEF8. Immunoblotting showed significantly increased protein levels of DEF8 in the substantia nigra and putamen of patients with PD and the temporal cortex of patients with DLB. In addition, the smear band of DEF8 appeared in the insoluble fraction where that of phosphorylated α-synuclein was detected. These findings indicate the involvement of DEF8 in the formation of Lewy bodies. Quantitative and qualitative alterations in DEF8 may reflect the dysregulation of autophagy in Lewy body diseases.

Aberrant functional connectivity within the salience network is related to cognitive deficits and disorganization in psychosis

In schizophrenia and schizoaffective disorder cognitive deficits are a reliable characteristic predicting a poor functional outcome. It has been theorized that both the default mode network (DMN) and the salience network (SN) play a crucial role in cognitive processes and aberrant functional connectivity within these networks in psychotic patients has been reported. The goal of this study was to reveal potential links between aberrant functional connectivity within these networks and impaired cognitive performance in psychosis.We chose two approaches for cognitive assessment, first the MATRICS Consensus Cognitive Battery (MCCB) combined into a global score and second the disorganization factor derived from a five-factor model of the Positive and Negative Syndrome Scale (PANSS) known to be relevant for cognitive performance. DMN and SN were identified using independent component analysis on resting-state functional magnetic resonance imaging data.We found significantly decreased connectivity within the right supplementary motor area (SMA) and bilateral putamen in patients with psychosis (n = 70; 27F/43M) compared to healthy controls (n = 72; 28F/44M). Within patients, linear regression analysis revealed that aberrant SMA connectivity was associated with impaired global cognition, while dysfunctional bilateral putamen connectivity predicted disorganization. There were no significant changes in connectivity within the DMN.Results support the hypothesis that SN dysfunctional connectivity is important in the pathobiology of cognitive deficits in psychosis. For the first time we were able to show the involvement of dysfunctional SMA connectivity in this context. We interpret the decreased SN connectivity as evidence of reduced functionality in recruiting brain areas necessary for cognitive processing.

Vitamin D and cardiometabolic outcomes in first episode psychosis (FEP): A prospective cohort study

In schizophrenia and schizoaffective disorder cognitive deficits are a reliable characteristic predicting a poor functional outcome. It has been theorized that both the default mode network (DMN) and the salience network (SN) play a crucial role in cognitive processes and aberrant functional connectivity within these networks in psychotic patients has been reported. The goal of this study was to reveal potential links between aberrant functional connectivity within these networks and impaired cognitive performance in psychosis.We chose two approaches for cognitive assessment, first the MATRICS Consensus Cognitive Battery (MCCB) combined into a global score and second the disorganization factor derived from a five-factor model of the Positive and Negative Syndrome Scale (PANSS) known to be relevant for cognitive performance. DMN and SN were identified using independent component analysis on resting-state functional magnetic resonance imaging data.We found significantly decreased connectivity within the right supplementary motor area (SMA) and bilateral putamen in patients with psychosis (n = 70; 27F/43M) compared to healthy controls (n = 72; 28F/44M). Within patients, linear regression analysis revealed that aberrant SMA connectivity was associated with impaired global cognition, while dysfunctional bilateral putamen connectivity predicted disorganization. There were no significant changes in connectivity within the DMN.Results support the hypothesis that SN dysfunctional connectivity is important in the pathobiology of cognitive deficits in psychosis. For the first time we were able to show the involvement of dysfunctional SMA connectivity in this context. We interpret the decreased SN connectivity as evidence of reduced functionality in recruiting brain areas necessary for cognitive processing.

Glutamate cycle changes in the putamen of patients with de novo Parkinson's disease using 1H MRS

IntroductionTo investigate glutamatergic metabolism changes in the putamen of patients with de novo Parkinson's Disease (PD) and test the hypothesis that glutamate (Glu) levels are abnormally elevated in the putamen contralateral to where the motor clinical signs predominate as expected from observations in animal models. Methods1H NMR spectra from 17 healthy control volunteers were compared with spectra from 17 de novo PD patients of who 14 were evaluated again after 2–3 years of disease progression. Statistical analysis used random-effects models. ResultsThe only significant difference between PD patients and controls was a higher glutamine (Gln) concentration in the putamen ipsilateral to the hemibody with predominant motor signs (Visit 1: 6.0 ± 0.4 mM vs. 5.2 ± 0.2 mM, p < 0.05; Visit 2: 6.2 ± 0.3 mM vs. 5.2 ± 0.2 mM, p < 0.05). At Visit 1, PD patients had higher Glu and Gln levels in the putamen ipsilateral versus contralateral to dominant clinical signs (Glu: 12.2 ± 0.6 mM vs. 10.4 ± 0.6 mM, p < 0.05; Gln: 6.0 ± 0.4 mM vs. 4.8 ± 0.4 mM, p < 0.05; Glu and Gln pool (Glx): 17.9 ± 0.8 mM vs. 14.7 ± 1.1 mM, p < 0.05). At Visit 2, the sum of the two metabolites remained significantly higher in the ipsilateral versus contralateral putamen (Glx: 18.3 ± 0.6 mM vs. 16.1 ± 0.9 mM, p < 0.05). ConclusionIn de novo PD patients, the putamen ipsilateral to the more affected hemibody showed elevated Gln versus controls and elevated Glu and Gln concentrations versus the contralateral side. Abnormalities in Glu metabolism therefore occur early in PD but unexpectedly in the putamen contralateral to the more damaged hemisphere, suggesting they are not dependent solely on dopamine loss.

Inverse Association Between Resting-State Putamen Activity and Iowa Gambling Task Performance in Patients With Obsessive-Compulsive Disorder and Control Subjects.

BackgroundSymptoms of obsessive-compulsive disorder (OCD) have been conceptualized as manifestations of decision-making deficits. Patients with OCD exhibit impairment during the decision-making process, as assessed by the Iowa Gambling Task (IGT). This impairment is independent of clinical severity and disease progression. However, the association between the decision-making deficit and resting-state brain activity of patients with OCD has not been examined.MethodsFifty unmedicated patients with OCD and 55 matched control subjects completed IGT. Resting-state brain activity was examined using the fractional amplitude of low-frequency fluctuations (fALFFs). fALFF analysis focused on the slow-4 and 5 bands. Group comparisons were performed to determine the association between IGT performance and fALFFs.ResultsThere was a significant group difference in the association between the IGT total net score and slow-4 fALFFs in the left putamen (voxel height threshold of p < 0.001; cluster size threshold of p < 0.05; family wise error-corrected). Higher putamen slow-4 fALFFs were correlated with lower IGT scores for OCD patients (r = −0.485; p < 0.0005) and higher IGT scores for control subjects (r = 0.402; p < 0.005). There was no group difference in the association between the IGT total net score and slow-5 fALFFs.ConclusionsThese findings in unmedicated patients demonstrate the importance of resting-state putamen activity for decision-making deficit associated with OCD, as measured by IGT. The inverse correlation may be explained by the hypersensitive response of the putamen in patients with OCD.

Combined Application of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Techniques to Investigate the Effect of Iron Deposition on Microstructural Changes in the Brain in Parkinson's Disease.

ObjectivesBrain iron deposition and microstructural changes in brain tissue are associated with Parkinson’s disease (PD). However, the correlation between these factors in Parkinson’s disease has been little studied. This study aimed to use quantitative susceptibility mapping combined with diffusion kurtosis imaging to investigate the effects of iron deposition on microstructural tissue alterations in the brain.MethodsQuantitative susceptibility mapping and diffusion kurtosis imaging were performed on 24 patients with early PD, 13 patients with advanced PD, and 25 healthy controls. The mean values of magnetic susceptibility and diffusion kurtosis were calculated for the bilateral substantia nigra, red nucleus, putamen, globus pallidus, and caudate nucleus, and compared between the groups. Correlation analyses between the diffusion kurtosis of each nucleus and its magnetic susceptibility parameters in PD patients and healthy controls were performed.ResultsThe study found a significant increase in iron deposition in the substantia nigra, red nucleus, putamen and globus pallidus, bilaterally, in patients with PD. Mean kurtosis values were increased in the substantia nigra but decreased in the globus pallidus; axial kurtosis values were decreased in both the substantia nigra and red nucleus; radial kurtosis values were increased in the substantia nigra but showed an opposite trend in the globus pallidus and caudate nucleus. In the substantia nigra of patients with PD, magnetic susceptibility was positively correlated with mean and radial kurtosis values, and negatively correlated with axial kurtosis. None of these correlations were significantly different in the control group. In the putamen, magnetic susceptibility was positively correlated with mean, axial, and radial kurtosis only in patients with advanced-stage PD.ConclusionOur study provides new evidence for brain iron content and microstructural alterations in patients with PD. Iron deposition may be a common mechanism for microstructural alterations in the substantia nigra and putamen of patients with PD. Tracking the dynamic changes in iron content and microstructure throughout the course of PD will help us to better understand the dynamics of iron metabolism and microstructural alterations in the pathogenesis of PD and to develop new approaches to monitor and treat PD.

Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation to cognitive functioning.

Background:Patients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but its role in deep gray matter (DGM) regions is unclear.Aims:To evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction, and post-processing techniques.Methods:A 7-Tesla magnetic resonance imaging scanner combined with a lipid suppression coil and subject-specific water suppression pulses was used to acquire high-resolution magnetic resonance spectroscopic imaging data. Tissue fraction correction and registration to a standard brain were performed for group comparison in specifically delineated DGM regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status.Results:Average glutamate levels across DGM structures (i.e. caudate, pallidum, putamen, and thalamus) in mostly medicated patients with a psychotic disorder (n = 16, age = 33, 4 females) were lower compared to healthy controls (n = 23, age = 24, 7 females; p = 0.005, d = 1.06). Stratified analyses showed lower glutamate levels in the caudate (p = 0.046, d = 0.76) and putamen p = 0.013, d = 0.94). These findings were largely explained by age differences between groups. DGM glutamate levels were positively correlated with psychomotor speed (r(30) = 0.49, p = 0.028), but not with other cognitive domains.Conclusions:We find reduced glutamate levels across DGM structures including the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Despite limitations concerning age differences, these results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in psychotic disorders.

A multi-pronged investigation of option generation using depression, PET and modafinil.

Option generation is a critical process in decision making, but previous studies have largely focused on choices between options given by a researcher. Consequently, how we self-generate options for behaviour remain poorly understood. Here, we investigated option generation in major depressive disorder and how dopamine might modulate this process, as well as the effects of modafinil (a putative cognitive enhancer) on option generation in healthy individuals. We first compared differences in self-generated options between healthy non-depressed adults [n = 44, age = 26.3 years (SD 5.9)] and patients with major depressive disorder [n = 54, age = 24.8 years (SD 7.4)]. In the second study, a subset of depressed individuals [n = 22, age = 25.6 years (SD 7.8)] underwent PET scans with 11C-raclopride to examine the relationships between dopamine D2/D3 receptor availability and individual differences in option generation. Finally, a randomized, double-blind, placebo-controlled, three-way crossover study of modafinil (100 mg and 200 mg), was conducted in an independent sample of healthy people [n = 19, age = 23.2 years (SD 4.8)] to compare option generation under different doses of this drug. The first study revealed that patients with major depressive disorder produced significantly fewer options [t(96) = 2.68, P = 0.009, Cohen's d = 0.54], albeit with greater uniqueness [t(96) = -2.54, P = 0.01, Cohen's d = 0.52], on the option generation task compared to healthy controls. In the second study, we found that 11C-raclopride binding potential in the putamen was negatively correlated with fluency (r = -0.69, P = 0.001) but positively associated with uniqueness (r = 0.59, P = 0.007). Hence, depressed individuals with higher densities of unoccupied putamen D2/D3 receptors in the putamen generated fewer but more unique options, whereas patients with lower D2/D3 receptor availability were likely to produce a larger number of similar options. Finally, healthy participants were less unique [F(2,36) = 3.32, P = 0.048, partial η2 = 0.16] and diverse [F(2,36) = 4.31, P = 0.021, partial η2 = 0.19] after taking 200 mg versus 100 mg and 0 mg of modafinil, while fluency increased linearly with dosage at a trend level [F(1,18) = 4.11, P = 0.058, partial η2 = 0.19]. Our results show, for the first time, that option generation is affected in clinical depression and that dopaminergic activity in the putamen of patients with major depressive disorder may play a key role in the self-generation of options. Modafinil was also found to influence option generation in healthy people by reducing the creativity of options produced.

Acupuncture Enhances Dorsal Raphe Functional Connectivity in Knee Osteoarthritis With Chronic Pain.

IntroductionKnee osteoarthritis is a common disease in the elderly. Patients suffer from long-term chronic pain and reduced life quality. Acupuncture has been proven to be an effective treatment for KOA. However, the neural mechanism of acupuncture is unclear, so far. Periaqueductal gray (PAG) and raphe nuclei (RPN) are essential structures associated with chronic pain in human brains. This study aims to investigate functional connectivity (FC) changes of PAG and RPN in KOA to interpret the neural mechanism of acupuncture.MethodsIn 15 patients with KOA and 15 healthy controls (HC), we acquired Visual Analog Scale (VAS) scores and resting-state fMRI images of each participant before and after acupuncture stimulation on EX-LE5 acupoint. Then, PAG and RPN were selected as seeds to perform FC analysis based on resting-state fMRI images. Finally, we compared FC patterns of PAG and RPN between patients with KOA and HC, then between pre-acupuncture and post-acupuncture. Correlations between FC values and VAS scores were calculated as well.ResultsFor PAG, FC of patients with KOA was lower in the right lingual gyrus at post-acupuncture compared with HC (p <0.001, uncorrected). For dorsal RPN, FC of patients with KOA was significantly higher in right putamen at post-acupuncture compared with HC (p <0.001, corrected with FDR), and FC changes were significant between pre-acupuncture and post-acupuncture in patients with KOA. Post-acupuncture FC values between dorsal RPN and right putamen were correlated with VAS scores. For medial RPN, FC of patients with KOA was lower in the right cerebellum at post-acupuncture compared with HC (p <0.001, uncorrected), but no significant FC changes were found between pre-acupuncture and post-acupuncture in patients with KOA. FC values between medial RPN and right cerebellum were not correlated with VAS scores at pre-acupuncture and post-acupuncture.DiscussionOur study demonstrated that acupuncture enhanced FC between dorsal RPN and the right putamen in patients with KOA, which was associated with chronic pain intensity. This result suggests that acupuncture stimulation can enhance FC between dorsal raphe and striatum, illustrating a neural mechanism that acupuncture can drive the patients' brain, with KOA, to perceive pain.

Iron Deposition in Gray Matter Nuclei of Patients With Intracranial Artery Stenosis: A Quantitative Susceptibility Mapping Study.

Purpose: This study aimed to use quantitative susceptibility mapping (QSM) to systematically investigate the changes of iron content in gray matter (GM) nuclei in patients with long-term anterior circulation artery stenosis (ACAS) and posterior circulation artery stenosis (PCAS).Methods: Twenty-five ACAS patients, 25 PCAS patients, and 25 age- and sex-matched healthy controls underwent QSM examination. Patients were scored using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) to assess the degree of neural function deficiency. On QSM images, iron related susceptibility of GM nuclei, including bilateral caudate nucleus, putamen (PU), globus pallidus (GP), thalamus (TH), substantia nigra (SN), red nucleus, and dentate nucleus (DN), were assessed. Susceptibility was compared between bilateral GM nuclei in healthy controls, ACAS patients, and PCAS patients. Partial correlation analysis, with age as a covariate, was separately performed to assess the relationships of susceptibility with NIHSS and mRS scores.Results: There were no significant differences between the susceptibilities for left and right hemispheres in all seven GM nucleus subregions for healthy controls, ACAS patients, and PCAS patients. Compared with healthy controls, mean susceptibility of bilateral PU, GP, and SN in ACAS patients and of bilateral PU, GP, SN, and DN in PCAS patients were significantly increased (all P < 0.05). In addition, mean susceptibility of bilateral TH and SN in PCAS patients was significantly higher than in ACAS patients (both P < 0.05). With partial correlation analysis, mean susceptibility at bilateral PU of ACAS patients was significantly correlated with mRS score (r = 0.415, P < 0.05), and at bilateral PU in PCAS patients was correlated with NIHSS score (r = 0.424, P < 0.05).Conclusion: Our findings indicated that abnormal iron metabolism may present in different subregions of GM nuclei after long-term ACAS and PCAS. In addition, iron content of PU in patients with ACAS and PCAS was correlated with neurological deficit scores. Therefore, iron quantification measured by QSM susceptibility may provide a new insight to understand the pathological mechanism of ischemic stroke caused by ACAS and PCAS.

Evaluating iron deposition in gray matter nuclei of patients with unilateral middle cerebral artery stenosis using quantitative susceptibility mapping

Iron mediated oxidative stress is involved in the process of brain injury after long-term ischemia. While increased iron deposition in the affected brain regions was observed in animal models of ischemic stroke, potential changes in the brain iron content in clinical patients with cerebral ischemia remain unclear. Quantitative susceptibility mapping (QSM), a non-invasive magnetic resonance imaging technique, can be used to evaluate iron content in the gray matter (GM) nuclei reliably. In this study, we aimed to quantitatively evaluate iron content changes in GM nuclei of patients with long-term unilateral middle cerebral artery (MCA) stenosis/occlusion-related cerebral ischemia using QSM.Forty-six unilateral MCA stenosis/occlusion patients and 38 age-, sex- and education-matched healthy controls underwent QSM. Clinical variables of history of hypertension, diabetes, hyperlipidemia, hyperhomocysteinemia, smoking, and drinking in all patients were evaluated. The iron-related susceptibility of GM nucleus subregions, including the bilateral caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus, substantia nigra (SN), red nucleus, and dentate nucleus, was assessed. Susceptibility was compared between the bilateral GM nuclei in patients and controls. Receiver operating characteristic curve analysis was used to evaluate the efficacy of QSM susceptibility in distinguishing patients with unilateral MCA stenosis/occlusion from healthy controls. Multiple linear regression analysis was used to evaluate the relationship between ipsilateral susceptibility levels and clinical variables.Except for the CN, the susceptibility in most bilateral GM nucleus subregions was comparable in healthy controls, whereas for patients with unilateral MCA stenosis/occlusion, the ipsilateral PU, GP, and SN exhibited significantly higher susceptibility than the contralateral side (all P < 0.05). Compared with controls, susceptibility of the ipsilateral PU, GP, and SN and of contralateral PU in patients were significantly increased (all P < 0.05). The area under the curve (AUC) was greater for the ipsilateral PU than for the GP and SN (AUC = 0.773, 0.662 and 0.681; all P < 0.05). Multiple linear regression analysis showed that the increased susceptibility of the ipsilateral PU was significantly associated with hypertension, of the ipsilateral GP associated with smoking, and of the ipsilateral SN associated with diabetes (all P < 0.05).Our findings provide support for abnormal iron accumulation in the GM nuclei after chronic MCA stenosis/occlusion and its correlation with some cerebrovascular disease risk factors. Therefore, iron deposition in the GM nuclei, as measured by QSM, may be a potential biomarker for long-term cerebral ischemia.

Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases.

Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas. The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated. In this observational study, we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases (LBDs) and Alzheimer disease (AD), shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration. We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival. Disease progression in LBDs correlated positively with poly (ADP-Ribose) and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts, indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes. Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and myeloperoxidase concentrations in the striatum, suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism of β-amyloid entering the mitochondria and subsequent free radicals generation. Patients with lower striatal 8-oxo-dG and myeloperoxidase levels had a survival advantage in AD. The age of onset also affected disease progression. Tissue requests for the postmortem biochemistry, genetics, and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center (ADRC) Biospecimens Committee (ethics approval reference number: T1705, approval date: August 6, 2019). Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health & Safety Biological Safety Committee (approval code: 3739, approval date: February 25, 2020). Radioactive Material Authorization was approved by the Washington University Environmental Health & Safety Radiation Safety Committee (approval code: 1056, approval date: September 18, 2019).

Diffusion-Weighted MRI Findings of Caudate Nucleus and Putamen in Patients With Obsessive-Compulsive Disorder.

ObjectiveThe purpose of this study was to establish the diffusion-weighted magnetic resonance imaging (DW-MRI) findings of the caudate nucleus and putamen in patients with obsessive-compulsive disorder (OCD) and to obtain new information on the etiopathogenesis of OCD, which is still unclear.MethodsThe study comprised 20 patients with OCDs and 20 healthy volunteers. In these cases, DW-MRI and diffusion-weighted echo-planar images (DW-EPI) at b600 and b1000 gradient values were taken and the measurements were made using the apparent diffusion coefficient (ADC) maps of each group at b600 and b1000 values from the caudate nucleus and putamen.ResultsWhen the DW-MRI examination in patients with OCD was compared with the control group, the mean ADC values in the caudate nucleus and putamen were not found to have statistically significantly changed. In addition, there were no significant differences regarding the right and left caudate nuclei and putamen ADC values at the b600 and b1000 in the patients with OCD or the control group.ConclusionThere are still many unknowns about the neurobiology of OCD. When the DW-MRI examination of the patients with OCD was compared with the control group in our study, no significant difference was found between the ADC values of the caudate nucleus and putamen. Further studies are required for this present study on DW-MRI in patients with OCD to be meaningful.

White Matter Hyperintensities of Bilateral Lenticular Putamen in Patients with Proliferative Diabetic Retinopathy: A Voxel-based Morphometric Study.

ObjectiveTo explore the changes in gray matter volume (GMV) and white matter volume (WMV) in proliferative diabetic retinopathy (PDR) patients using voxel-based morphometry (VBM).Participants and MethodsIn total, 15 patients (10 males, 5 females) with PDR were enrolled to the patient group and 15 healthy controls (10 males, 5 females) to the control group, matched for age, sex, handedness, and education status. All individuals underwent voxel-based morphometry scans. GMV and WMV were compared between the two groups.ResultsGMV in bilateral superior temporal gyrus, sixth area of left cerebellum, left middle temporal gyrus, left orbital inferior frontal gyrus and left middle cingulum gyrus and WMV in left thalamus and left precuneus were significantly lower in patients than controls (P<0.01). Conversely, WMV was significantly higher in bilateral lenticular putamen of patients than controls (P<0.01).ConclusionAbnormal GMV and WMV in many specific areas of the cerebrum provide new insights for exploration of the occurrence and development of DR and its pathophysiology.

Regulatory miRNA-mRNA Networks in Parkinson's Disease.

Parkinson’s disease (PD) is the second-most common neurodegenerative disease, and its pathophysiology is associated with alpha-synuclein accumulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. MicroRNAs are small non-coding RNAs that regulate gene expression, and many previous studies have described their dysregulation in plasma, CSF, and in the brain of patients with PD. In this study, we aimed to provide a regulatory network analysis on differentially expressed miRNAs in the brain of patients with PD. Based on our systematic review with a focus on the substantia nigra and the putamen, we found 99 differentially expressed miRNAs in brain samples from patients with PD, which regulate 135 target genes. Five genes associated with neuronal survival (BCL2, CCND1, FOXO3, MYC, and SIRT1) were modulated by dysregulated miRNAs found in the substantia nigra and the putamen of patients with PD. The functional enrichment analysis found FoxO and PI3K-AKT signaling as pathways related to PD. In conclusion, our comprehensive analysis of brain-related miRNA–mRNA regulatory networks in PD showed that mechanisms involving neuronal survival signaling, such as cell cycle control and regulation of autophagy/apoptosis, may be crucial for the neurodegeneration of PD, being a promising way for novel disease-modifying therapies.