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Mild cognitive impairment (MCI), a well-defined nonmotor manifestation of Parkinson's disease (PD), greatly impairs functioning and quality of life. However, the contribution of cerebral perfusion, quantified by arterial spin labeling (ASL), to MCI in PD remains poorly understood. The selection of an optimal delay time is difficult for single-delay ASL, a problem which is avoided by multidelay ASL. This study uses a multidelay multiparametric ASL to investigate cerebral perfusion including cerebral blood flow (CBF) and arterial transit time (ATT) in early stage PD patients exhibiting MCI using a voxel-based brain analysis. Magnetic resonance imaging data were acquired on a 3.0 T system at rest in 39 early stage PD patients either with MCI (PD-MCI, N = 22) or with normal cognition (PD-N, N = 17), and 36 age- and gender-matched healthy controls (HCs). CBF and ATT were compared among the three groups with SPM using analysis of variance followed by post hoc analyses to define regional differences and examine their relationship to clinical data. PD-MCI showed prolonged ATT in right thalamus compared to both PD-N and HC, and in right supramarginal gyrus compared to HC. PD-N showed shorter ATT in left superior frontal cortex compared to HC. Prolonged ATT in right thalamus was negatively correlated with the category fluency test (p = .027, r = -0.495) in the PD-MCI group. This study shows that ATT may be a more sensitive marker than CBF for the MCI, and highlights the potential role of thalamus and inferior parietal region for MCI in early stage PD., (© 2018 Wiley Periodicals, Inc.)

Purpose To use resting-state functional magnetic resonance (MR) imaging and graph theory approaches to investigate the brain functional connectome and its potential relation to disease severity in Parkinson disease (PD). Materials and Methods This case-control study was approved by the local research ethics committee, and all participants provided informed consent. There were 153 right-handed patients with PD and 81 healthy control participants recruited who were matched for age, sex, and handedness to undergo a 3-T resting-state functional MR examination. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and the topologic properties were analyzed by using graph theory approaches. Nonparametric permutation tests were used to compare topologic properties, and their relationship to disease severity was assessed. Results The functional connectome in PD showed abnormalities at the global level (ie, decrease in clustering coefficient, global efficiency, and local efficiency, and increase in characteristic path length) and at the nodal level (decreased nodal centralities in the sensorimotor cortex, default mode, and temporal-occipital regions; P < .001, false discovery rate corrected). Further, the nodal centralities in left postcentral gyrus and left superior temporal gyrus correlated negatively with Unified Parkinson's Disease Rating Scale III score (P = .038, false discovery rate corrected, r = -0.198; and P = .009, false discovery rate corrected, r = -0.270, respectively) and decreased with increasing Hoehn and Yahr stage in patients with PD. Conclusion The configurations of brain functional connectome in patients with PD were perturbed and correlated with disease severity, notably with those responsible for motor functions. These results provide topologic insights into understanding the neural functional changes in relation to disease severity of PD. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on September 11, 2017.

Patients with Parkinson's disease with mild cognitive impairment (PD‐M) progress to dementia more frequently than those with normal cognition (PD‐N), but the underlying neurobiology remains unclear. This study aimed to define the specific morphological brain network alterations in PD‐M, and explore their potential diagnostic value. Twenty‐four PD‐M patients, 17 PD‐N patients, and 29 healthy controls (HC) underwent a structural MRI scan. Similarity between interregional gray matter volume distributions was used to construct individual morphological brain networks. These were analyzed using graph theory and network‐based statistics (NBS), and their relationship to neuropsychological tests was assessed. Support vector machine (SVM) was used to perform individual classification. Globally, compared with HC, PD‐M showed increased local efficiency (p =.001) in their morphological networks, while PD‐N showed decreased normalized path length (p =.008). Locally, similar nodal deficits were found in the rectus and lingual gyrus, and cerebellum of both PD groups relative to HC; additionally in PD‐M nodal deficits involved several frontal and parietal regions, correlated with cognitive scores. NBS found that similar connections were involved in the default mode and cerebellar networks of both PD groups (to a greater extent in PD‐M), while PD‐M, but not PD‐N, showed altered connections involving the frontoparietal network. Using connections identified by NBS, SVM allowed discrimination with high accuracy between PD‐N and HC (90%), PD‐M and HC (85%), and between the two PD groups (65%). These results suggest that default mode and cerebellar disruption characterizes PD, more so in PD‐M, whereas frontoparietal disruption has diagnostic potential. [ABSTRACT FROM AUTHOR]

While previous structural-covariance studies have an advanced understanding of brain alterations in Parkinson's disease (PD), brain–behavior relationships have not been examined at the individual level. This study investigated the topological organization of grey matter (GM) networks, their relation to disease severity, and their potential imaging diagnostic value in PD. Fifty-four early-stage PD patients and 54 healthy controls (HC) underwent structural T1-weighted magnetic resonance imaging. GM networks were constructed by estimating interregional similarity in the distributions of regional GM volume using the Kullback–Leibler divergence measure. Results were analyzed using graph theory and network-based statistics (NBS), and the relationship to disease severity was assessed. Exploratory support vector machine analyses were conducted to discriminate PD patients from HC and different motor subtypes. Compared with HC, GM networks in PD showed a higher clustering coefficient (P = 0.014) and local efficiency (P = 0.014). Locally, nodal centralities in PD were lower in postcentral gyrus and temporal-occipital regions, and higher in right superior frontal gyrus and left putamen. NBS analysis revealed decreased morphological connections in the sensorimotor and default mode networks and increased connections in the salience and frontoparietal networks in PD. Connection matrices and graph-based metrics allowed single-subject classification of PD and HC with significant accuracy of 73.1 and 72.7%, respectively, while graph-based metrics allowed single-subject classification of tremor-dominant and akinetic–rigid motor subtypes with significant accuracy of 67.0%. The topological organization of GM networks was disrupted in early-stage PD in a way that suggests greater segregation of information processing. There is potential for application to early imaging diagnosis. [ABSTRACT FROM AUTHOR]

• Patients with FOG exhibited a disrupted topological organization of functional brain networks. • Nodal centralities and functional connectivity increased in widely distributed networks in PD patients with FOG. • The altered nodal centralities in the right hippocampus were positively correlated with FOG severity. Freezing of gait (FOG) is a common and debilitating gait disturbance in patients with Parkinson's disease (PD), but the potential mechanisms are still unclear. This study aimed to explore alterations in the topological organization of whole-brain functional networks in PD patients with FOG. We recruited 75 patients with PD, 37 patients with FOG and 38 patients without FOG, to undergo resting-state functional magnetic resonance imaging (fMRI). The whole-brain functional networks were constructed, and the topological properties at three (global, nodal, and connectional) levels were analyzed using graph theory approaches. Compared with patients without FOG, patients with FOG exhibited altered global topological properties (a significant decrease in the normalized clustering coefficient and small-worldness), implying a shift toward randomization in their functional brain networks. At the node and connectional levels, patients with FOG showed increased nodal centralities and functional connectivity in the sensorimotor network, frontoparietal network, visual network, subcortical and limbic regions, and decreased nodal centralities in the frontoparietal network and the cerebellum. Furthermore, the altered nodal centralities in the right hippocampus (HIP) were positively correlated with FOG severity. This study suggests that FOG in PD is associated with disrupted topological organization of whole-brain functional networks, involving dysfunction of the multiple networks. [ABSTRACT FROM AUTHOR]

Background: Several biallelic truncating and missense variants of the gem nuclear organelle–associated protein 5 (GEMIN5) gene have been reported to cause neurodevelopmental disorders characterized by cerebellar atrophy, intellectual disability, and motor dysfunction. However, the association between biallelic GEMIN5 variants and early‐infantile developmental and epileptic encephalopathies (EIDEEs) has not been reported. Purpose: This study aimed to expand the phenotypic spectrum of GEMIN5 and explore the correlations between epilepsy and molecular sub‐regional locations. Methods: We performed whole‐exome sequencing in two patients with EIDEE with unexplained etiologies. The damaging effects of variants were predicted using multiple in silico tools and modeling. All reported patients with GEMIN5 pathogenic variants and detailed neurological phenotypes were analyzed to evaluate the genotype–phenotype relationship. Results: Novel biallelic GEMIN5 variants were identified in two unrelated female patients with EIDEE, including a frameshift variant (Hg19, chr5:154284147‐154284148delCT: NM_015465: c.2551_c.2552delCT: p.(Leu851fs*30)), a nonsense mutation (Hg19, chr5:154299603‐154299603delTinsAGA: NM_015465: c.1523delTinsAGA: p.(Leu508*)), and two missense variants (Hg19, chr5:154282663T > A: NM_015465: c.2705T > A: p.(Leu902Gln) and Hg19, chr5:154281002C > G: NM_015465: c.2911C > G: p.(Gln971Glu)), which were inherited from asymptomatic parents and predicted to be damaging or probably damaging using in silico tools. Except p.Leu508*, all these mutations are located in tetratricopeptide repeat (TPR) domain. Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia. Video electroencephalogram showed suppression‐bursts. Through a literature review, we found 5 published papers reporting 48 patients with biallelic variants in GEMIN5. Eight of 48 patients have epilepsy, and 5 patients started before 1 year old, which reminds us of the relevance between GEMIN5 variants and EIDEE. Further analysis of the 49 GEMIN5 variants in those 50 patients demonstrated that variants in TPR‐like domain or RBS domain were more likely to be associated with epilepsy. Conclusions: We found novel biallelic variants of GEMIN5 in two individuals with EIDEE and expanded the clinical phenotypes of GEMIN5 variants. It is suggested that the GEMIN5 gene should be added to the EIDEE gene panel to aid in the clinical diagnosis of EIDEE and to help determine patient prognosis. [ABSTRACT FROM AUTHOR]

In this study, poly (ε-caprolactone) (PCL) microspheres loading magnetic Fe 3 O 4 nanoparticles and anti-cancer drug of doxorubicin hydrochloride (DOX) were successfully prepared by a modified solvent-evaporation method. The obtained magnetic composite microspheres exhibited dual features of magnetic resonance imaging and controlled drug delivery. The morphology, structure, thermal behavior and magnetic properties of the drug-loaded magnetic microspheres were investigated in detail by SEM, XRD, DSC and SQUID. The obtained composite microspheres showed superparamagnetic behavior and T 2 -weighted enhancement effect. The drug loading, encapsulation efficiency, releasing behavior and in vitro cytotoxicity of the drug-loaded composite microspheres were systematically investigated. It was found that the values of drug loading and encapsulation efficiency were 36.7% and 25.8%, respectively. The composite microspheres were sensitive to pH and released in a sustained way, and both the release curves under various pH conditions (4.0 and 7.4) were well satisfied with the biphase kinetics function. In addition, the magnetic response of the drug-loaded microspheres was studied and the results showed that the composite microspheres had a good magnetic stability and strong targeting ability. [ABSTRACT FROM AUTHOR]