Abnormalities in spontaneous brain activity and functional connectivity are associated with cognitive impairments in children with type 1 diabetes mellitus.

BACKGROUND: It remains unclear whether alterations in brain function occur in the early stage of pediatric type 1 diabetes mellitus(T1DM). We aimed to examine changes in spontaneous brain activity and functional connectivity (FC) in children with T1DM using resting-state functional magnetic resonance imaging (rs-fMRI), and to pinpoint potential links between neural changes and cognitive performance. METHODS: In this study, 22 T1DM children and 21 age-, sex-matched healthy controls underwent rs-fMRI. The amplitude of low frequency fluctuations (ALFF) and seed-based FC analysis were performed to examine changes in intrinsic brain activity and functional networks in T1DM children. Partial correlation analyses were utilized to explore the correlations between ALFF values and clinical parameters. RESULTS: The ALFF values were significantly lower in the lingual gyrus (LG) and higher in the left medial superior frontal gyrus (MSFG) in T1DM children compared to controls. Subsequent FC analysis indicated that the LG had decreased FC with bilateral inferior occipital gyrus, and the left MSFG had decreased FC with right precentral gyrus, right inferior parietal gyrus and right postcentral gyrus in children with T1DM. The ALFF values of LG were positively correlated with full-scale intelligence quotient and age at disease onset in T1DM children, while the ALFF values of left MSFG were positively correlated with working memory scores. CONCLUSION: Our findings revealed abnormal spontaneous activity and FC in brain regions related to visual, memory, default mode network, and sensorimotor network in the early stage of T1DM children, which may aid in further understanding the mechanisms underlying T1DM-associated cognitive dysfunction.

Altered gray matter volume in children with newly diagnosed type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) affects the development of cognitive function in children, which may be due to deficits in brain structures or functions. It is unclear whether children with T1DM experience alterations in the gray matter (GM) structure at the initial stages of the disease. This study investigated GM structure alterations in children with newly diagnosed T1DM. METHODS: Based on 3D T1-weighted MR images, we investigated the gray matter volume (GMV) of 35 newly diagnosed T1DM children and 35 age- and sex-matched healthy controls using voxel-based morphometry. The brain regions with significant differences in GMV between the newly diagnosed T1DM children and the controls were extracted and the correlation with clinical data was assessed. RESULTS: Compared with the control group, children with newly diagnosed T1DM had a lower GMV in the right inferior and middle temporal gyri, right lingual gyrus, and left superior frontal gyrus. In T1DM subjects, the GMV of the right middle temporal gyrus was positively correlated with IQ but was negatively correlated with HbA1c. CONCLUSIONS: Our findings provide compelling evidence that GM abnormalities occur during early disease stages in T1DM children, which may be a potential neurobiological mechanism underlying cognitive deficits. IMPACT: Using an efficient method to analyze gray matter changes in T1DM is very important. The anterior, posterior, and temporal brain regions are susceptible to T1DM in children. Recent glucose variability may affect regional gray matter volume in children with newly diagnosed T1DM. Structural changes were documented in the gray matter of the brain even at the early stages of the disease in children with T1DM.

Disruption of brain regional homogeneity and functional connectivity in male NAFLD: evidence from a pilot resting-state fMRI study.

BACKGROUND: The neurophysiological mechanisms underlying cognitive deficits in non-alcoholic fatty liver disease (NAFLD) remain unknown. Cognitive changes may be caused by brain alterations in neural activity and functional connectivity (FC). AIM: This study aims to investigate the alterations between spontaneous brain neural activity and FC in male NAFLD patients and the relationship of neural activity with cognitive performance. METHODS: In this prospective study, 33 male pre-cirrhosis NAFLD subjects and 20 male controls matched for age, education level, and body mass index. All participants underwent resting-state functional magnetic resonance imaging scans and neuropsychological examinations. Regional homogeneity (ReHo) analysis was used to investigate the brain function in NAFLD, and regions with significantly altered ReHo were selected as seeds for subsequent FC analysis. Partial correlation analysis was used to assess the relationships between altered ReHo measures and cognitive performance indicators. RESULTS: Compared with the controls, the NAFLD patients showed increased ReHo in the opercular part of the right inferior frontal gyrus (IFGoperc) and decreased ReHo in the right middle frontal gyrus (MFG) and left superior parietal gyrus (SPG). The subsequent FC analysis showed increased FC between these regions (right IFGoperc, right MFG, and left SPG) and nodes of the default mode network (DMN) (such as left supraMarginal, left median cingulate and paracingulate gyri, left precuneus, orbital part of left medial frontal gyrus, and bilateral posterior cingulate gyrus). In addition, significant positive correlations were observed between NAFLD patients' clock drawing test scores and altered ReHo in prefrontal cortices (right IFGoperc and right MFG). CONCLUSION: Before developing cirrhosis, NAFLD patients showed altered neural activity in several brain regions and altered FC between the salience network and DMN. These alterations could potentially be a compensatory mechanism to maintain cognitive function in pre-cirrhosis NAFLD patients.

Altered Brain Glymphatic Function at Diffusion-Tensor MRI in Pre-cirrhotic Metabolic Dysfunction-Associated Fatty Liver Disease.

RATIONALE AND OBJECTIVES: To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. MATERIALS AND METHODS: A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. RESULTS: MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = -0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = -0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (-23.853 [-45.417, -2.289], P = 0.030) in MAFLD with MetS group. CONCLUSION: MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS.

Nomogram for Quantitatively Estimating the Risk of Fibrosis Progression in Type 2 Diabetic Patients With Nonalcoholic Fatty Liver Disease: A Pilot Study.

Background: Correct identification of the fibrosis progression risk is a critical step in the management of patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), because liver fibrosis, especially advanced liver fibrosis, is difficult to reverse. However, the progression of liver fibrosis is typically unnoticeable, leading to many patients failing to adhere to long-term therapeutic interventions. Reliable clinical tools for the quantification of the fibrosis progression risk may have effects on following long-term therapeutic recommendations to avoid further liver injury. Objective: This study aims to develop a nomogram for quantitatively estimating the risk of fibrosis progression in T2DM patients with NAFLD during lifestyle intervention. Methods: A total of 432 medical records of T2DM patients with NAFLD were retrospectively analyzed in this study. We divided patients into the progression and no-progression groups according to whether the value of liver stiffness measurement (LSM) increased by > 2 kPa at the last visit. The independent factors associated with the fibrosis progression, which were screened by univariate and multivariate Logistic regression, constituted the nomogram to determine the likelihood of fibrosis progression in T2DM patients with NAFLD. Results: Sixty-five of the 432 individuals (15%) were found to have fibrosis progression. Changes in body mass index [odds ratio (OR) = 1.586], glycosylated hemoglobin A1c (OR = 6.636), alanine aminotransferase (OR = 1.052), and platelet counts (OR = 0.908) were independently associated with fibrosis progression (all P < 0.05) and functioned as components of the newly developed nomogram. It showed satisfied discrimination and calibration after 1,000 bootstrapping. The DCA indicated that the nomogram yielded clinical net benefit when the threshold probability was < 0.8. Conclusion: We developed a nomogram incorporating dynamic alterations in clinical features to estimate the risk of fibrosis progression in T2DM patients with NAFLD, which aids the patients' compliance with long-term life interventions while allowing for prompt intervention adjustments.

Disrupted Regional Cerebral Blood Flow in Children With Newly-Diagnosed Type 1 Diabetes Mellitus: An Arterial Spin Labeling Perfusion Magnetic Resonance Imaging Study.

Object: Diabetes is associated with cerebral vascular dysfunction and increased vascular cognitive impairment. The objective of this study was to use arterial spin labeling (ASL) perfusion-weighted magnetic resonance imaging to investigate whether cerebral perfusion was changed in newly-diagnosed children with type 1 diabetes mellitus (T1DM) and the possible relationship between aberrant cerebral blood flow (CBF) with cognitive as well as clinical variables. Methods: Between January 2017 and February 2018, 34 children with newly-diagnosed T1DM and 34 age, gender, and education-matched healthy controls were included. Three dimensional pseudo-continuous ASL perfusion MRI was used to evaluate CBF. A conventional T2WI sequence was added to exclude intracranial disease. Regions with CBF differences between T1DM children and the controls were detected via voxel-wise comparisons in REST software. Associations among the result of neuropsychological test, clinical variables, and CBF values of different brains were investigated by using partial correlation analysis. Results: Compared with the controls, T1DM children show decreased CBF in the left calcarine and postcentral gyrus, and right precentral gyrus. The perfusion in the postcentral gyrus was positively correlated with IQ performance. No significant correlations were found between CBF and HbA1c, blood glucose level before imaging and IQ in other brain regions in T1DM children. Conclusion: There is an abnormal cerebral perfusion in children with newly diagnosed T1DM. The visual and sensorimotor areas are brain areas where perfusion is prone to change at the beginning of T1DM. Our study provided clues for cerebral pathophysiological changes in the initial stage of T1DM.

Abnormal Functional Connectivity Density in New-Onset Type 1 Diabetes Mellitus Children: A Resting-State Functional Magnetic Resonance Imaging Study.

Type 1 diabetes mellitus (T1DM) causes cognitive changes in children, which may be due to deficits in brain functions. It is unclear whether T1DM children will have brain functional changes during the initial stage of the disease. We aimed to investigate the changes in the functional brain network topology in children with new-onset T1DM. In this study, 35 new-onset T1DM children and 33 age-, sex-matched healthy controls underwent resting-state fMRI. The whole brain functional connectivity density (FCD) analysis and seed-based functional connectivity (FC) analysis were performed to investigate the changes in functional brain networks in new-onset T1DM children when compared with the controls. Pearson correlational analysis was used to explore the correlation between FCD value of differential brain areas and clinical variables in T1DM children. Compared with the controls, children with new-onset T1DM exhibited significantly decreased FCDs of the right inferior temporal gyrus (ITG) and the right posterior cingulate cortex (PCC). In the subsequent FC analysis, decreased FC was found between right PCC and right cuneus and increased FC was found between right ITG and left orbital part of inferior frontal gyrus in children with new-onset T1DM compared to the controls. The FCD values of right ITG and PCC did not correlate with HbA1c, blood glucose level before imaging, and full-scale intelligence quotient (IQ) in T1DM children. These results revealed that T1DM affect the functional activity of the immature brain at the initial stage. These findings also indicate a decrease in regional brain function and abnormalities in temporal-frontal and limbic-occipital circuitry in children with new-onset T1DM, and highlight the effects of T1DM on children's brain networks involved in visual process and memory, which may contribute to the cognition impairments observed in children with T1DM.

Clinical Value of Dorsal Medulla Oblongata Involvement Detected With Conventional Magnetic Resonance Imaging for Prediction of Outcome in Children With Enterovirus 71-Related Brainstem Encephalitis.

BACKGROUND: Brainstem encephalitis is the most common neurologic complication after enterovirus 71 infection. The involvement of brainstem, especially the dorsal medulla oblongata, can cause severe sequelae or death in children with enterovirus 71 infection. We aimed to determine the prevalence of dorsal medulla oblongata involvement in children with enterovirus 71-related brainstem encephalitis (EBE) by using conventional magnetic resonance imaging (MRI) and to evaluate the value of dorsal medulla oblongata involvement in outcome prediction. METHODS: Forty-six children with EBE were enrolled in the study. All subjects underwent a 1.5 Tesla MRI examination of the brain. The disease distribution and clinical data were collected. Dichotomized outcomes (good vs. poor) at longer than 6 months were available for 28 patients. Logistic regression was used to determine whether the MRI-confirmed dorsal medulla oblongata involvement resulted in improved clinical outcome prediction when compared with other location involvement. RESULTS: Of the 46 patients, 35 had MRI evidence of dorsal medulla oblongata involvement, 32 had pons involvement, 10 had midbrain involvement and 7 had dentate nuclei involvement. Patients with dorsal medulla oblongata involvement or multiple area involvement were significantly more often in the poor outcome group than in the good outcome group. Logistic regression analysis showed that dorsal medulla oblongata involvement was the most significant single variable in outcome prediction (predictive accuracy, 90.5%), followed by multiple area involvement, age and initial Glasgow Coma Scale score. CONCLUSIONS: Dorsal medulla oblongata involvement on conventional MRI correlated significantly with poor outcomes in EBE children, improved outcome prediction when compared with other clinical and disease location variables, and was most predictive when combined with multiple area involvement, Glasgow Coma Scale score and age.

Voxel-based morphometry reveals regional reductions of gray matter volume in school-aged children with short-term type 1 diabetes mellitus.

Follow-up observation is needed for type 1 diabetes mellitus (T1DM) children due to the potential injury to the brain. However, the effect of short-term T1DM on gray matter in school-aged children is still unclear. This study aimed to evaluate gray matter volume (GMV) changes and their relationships with clinical variables in school-aged children with short-term T1DM. Twenty-one school-aged T1DM children were compared with 21 control patients, matched for sex and age. T1-weighted gradient echo three-dimensional MRI was performed using a 3.0-Tesla scanner and the resulting images were processed with FSL software to assess the difference in GMV between the two groups. The children with T1DM presented with decreased GMV in the left middle temporal gyrus (LMTG), the right postcentral gyrus, and the left triangular part of the frontal inferior gyrus (LTP-FIG). No significant changes in intelligence quotient (IQ) were found between the T1DM and control groups. In T1DM patients, there was a significant positive correlation between the GMV of LMTG and full-scale IQ or linguistic IQ. In addition, an increased glycosylated hemoglobin level was negatively correlated with reduced GMV in the LMTG and LTP-FIG in the T1DM group. These findings suggest that short-term T1DM could lead to regional structural brain deficits in school-aged children. The GMV of the LMTG may affect IQ, and poor recent glycemic control may have an adverse effect on GMV in the LMTG and LTP-FIG in T1DM children.Video abstract: http://links.lww.com/WNR/A506.