Introduction: Alport syndrome (AS) is an inherited kidney disease with significant clinical heterogeneity. Prognosis prediction and risk assessment are important to assist patient care. However, a predictive tool of disease progression is still lacking. Methods: The prediction model was developed in 363 patients (124 kidney failure events) with X-linked AS (XLAS) from a single-center retrospective cohort study and validated in 2 external cohorts, including 193 (27 events) and 125 patients (33 events) with XLAS from 6 centers and the literature database, respectively. Cox proportional hazards regression analysis with stepwise selection was used to select the important variables related to the progression to kidney failure, by using the baseline demographic, clinical, and genetic data. The performance of the prediction model was evaluated and compared using receiver-operating characteristic (ROC) curve and calibration plot. Results: There were 4 variables identified that were significantly associated with the progression to kidney failure in the final model, namely sex, proteinuria, estimated glomerular filtration rate (eGFR), and pathogenic variants in COL4A5. Based on the model risk stratification, the median age at kidney failure was 23, 30, and 61 years in the low-, intermediate-, and high-risk groups, respectively. This model shows the best discrimination in predicting the progression to kidney failure before the age of 30 years, with areas under the curve (AUCs) > 0.80 in both development and external cohorts. Conclusion: A prediction model of progression to kidney failure based on clinical characteristics and genetic variants was developed and validated in patients with XLAS.

The study aimed to investigate the neurovascular coupling abnormalities in Leber’s hereditary optic neuropathy (LHON) and their associations with clinical manifestations. Twenty qualified acute Leber’s hereditary optic neuropathy (A-LHON, disease duration ≤ 1 year), 29 chronic Leber’s hereditary optic neuropathy (C-LHON, disease duration > 1 year), as well as 37 healthy controls (HCs) were recruited. The neurovascular coupling strength was quantified as the ratio between regional homogeneity (ReHo), which represents intrinsic neuronal activity and relative cerebral blood flow (CBF), representing microcirculatory blood supply. A one-way analysis of variance was used to compare intergroup differences in ReHo/CBF ratio with gender and age as co-variables. Pearson’s Correlation was used to clarify the association between ReHo, CBF, and neurovascular coupling strength. Furthermore, we applied linear and exponential non-linear regression models to explore the associations among ReHo/CBF, disease duration, and neuro-ophthalmological metrics. Compared with HCs, A_LHON, and C_LHON patients demonstrated a higher ReHo/CBF ratio than the HCs in the bilateral primary visual cortex (B_CAL), which was accompanied by reduced CBF while preserved ReHo. Besides, only C_LHON had a higher ReHo/CBF ratio and reduced CBF in the left middle temporal gyrus (L_MTG) and left sensorimotor cortex (L_SMC) than the HCs, which was accompanied by increased ReHo in L_MTG (p < 1.85e–3, Bonferroni correction). A-LHON and C-LHON showed a negative Pearson correlation between ReHo/CBF ratio and CBF in B_CAL, L_SMC, and L_MTG. Only C_LHON showed a weak positive correlation between ReHo/CBF ratio and ReHo in L_SMC and L_MTG (p < 0.05, uncorrected). Finally, disease duration was positively correlated with ReHo/CBF ratio of L_SMC (Exponential: Radj2 = 0.23, p = 8.66e–4, Bonferroni correction). No statistical correlation was found between ReHo/CBF ratio and neuro-ophthalmological metrics (p > 0.05, Bonferroni correction). Brain neurovascular “dyscoupling” within and outside the visual system might be an important neurological mechanism of LHON.

Purpose: The study aimed to unravel abnormal cerebral blood flow (CBF) in patients with Leber's hereditary optic neuropathy (LHON) using arterial spin labeling (ASL) and to investigate the associations among disrupted CBF, disease duration, and neuro-ophthalmological impairment. Methods: ASL perfusion imaging data was collected from 20 patients with acute LHON, 29 patients with chronic LHON, and 37 healthy controls. We used a one-way analysis of covariance to test the intergroup differences in CBF. Linear and nonlinear curve fit models were applied to explore the associations among CBF, disease duration, and neuro-ophthalmological metrics. Results: Brain regions differed in LHON patients, including the left sensorimotor and bilateral visual areas (p < 0.05, cluster-wise family-wise error correction). Acute and chronic LHON patients demonstrated lower CBF in bilateral calcarine than the healthy controls. Chronic LHON had lower CBF in the left middle frontal gyrus and sensorimotor cortex, and temporal-partial junction than the healthy controls and acute LHON. A significant logarithmic negative correlation was shown between CBF of left middle frontal gyrus and disease duration. A significant linear positive correlation was found between retinal nerve fiber layer thickness and CBF in left middle frontal gyrus, and negative correlations between loss of variance and CBF in left middle frontal gyrus and sensorimotor cortex (p < 0.05, Bonferroni correction). Conclusion: LHON patients exhibited reduced CBF in the visual pathway, sensorimotor and higher-tier cognitive areas. Disease duration and neuro-ophthalmological impairments can influence the metabolism of non-visual areas.

PurposeThe aim of this study was to investigate the brain gray matter volume (GMV) and spontaneous functional connectivity (FC) changes in patients with chronic Leber's hereditary optic neuropathy (LHON), and their relations with clinical measures.MethodsA total of 32 patients with chronic LHON and matched sighted healthy controls (HC) underwent neuro-ophthalmologic examinations and multimodel magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) was used to detect the GMV differences between the LHON and HC. Furthermore, resting-state FC analysis using the VBM-identified clusters as seeds was carried out to detect potential functional reorganization in the LHON. Finally, the associations between the neuroimaging and clinical measures were performed.ResultsThe average peripapillary retinal nerve fiber layer (RNFL) thickness of the chronic LHON was significantly thinner (T = −16.421, p < 0.001), and the mean defect of the visual field was significantly higher (T = 11.28, p < 0.001) than the HC. VBM analysis demonstrated a significantly lower GMV of bilateral calcarine gyri (CGs) in the LHON than in the HC (p < 0.05). Moreover, in comparison with the HC, the LHON had significantly lower FC between the centroid of the identified left CG and ipsilateral superior occipital gyrus (SOG) and higher FC between this cluster and the ipsilateral posterior cingulate gyrus (p < 0.05, corrected). Finally, the GMV of the left CG was negatively correlated with the LHON duration (r = −0.535, p = 0.002), and the FC between the left CG and the ipsilateral posterior cingulate gyrus of the LHON was negatively correlated with the average peripapillary RNFL thickness (r = −0.522, p = 0.003).ConclusionThe atrophied primary visual cortex of the chronic LHON may be caused by transneuronal degeneration following the retinal damage. Moreover, our findings suggest that the functional organization of the atrophied primary visual cortex has been reshaped in the chronic LHON.

Student financial assistance in Colleges and universities is an important part of the overall deployment of "targeted poverty alleviation". In order to understand the current situation of financial aid in Colleges and universities and put forward the corresponding countermeasures, a questionnaire was designed based on the identification of poor students, the form of financial aid, psychological assistance and the effect of financial aid. According to the results, using the thought of syndrome differentiation and treatment of traditional Chinese medicine, the concept of combination of disease and syndrome, three factors and so on is applied to the identification and funding of poor students, so as to promote the innovative development of funding education in colleges and universities.

Objective The purpose of this study was to investigate whether the large-scale structural rich club organization was abnormal in patients with Leber's hereditary optic neuropathy (LHON) using diffusion tensor imaging (DTI), and the associations among disrupted brain structural connectivity, disease duration, and neuro-ophthalmological impairment. Methods Nineteen acute, 34 chronic LHON patients, and 36 healthy controls (HC) underwent DTI and neuro-ophthalmological measurements. The brain structural network and rich club organization were constructed based on deterministic fiber tracking at the individual level. Then intergroup differences among the acute, chronic LHON patients and healthy controls (HC) in three types of structural connections, including rich club, feeder, and local ones, were compared. Network-based Statistics (NBS) was also used to test the intergroup connectivity differences for each fiber. Several linear and nonlinear curve fit models were applied to explore the associations among large-scale brain structural connectivity, disease duration, and neuro-ophthalmological metrics. Results Compared to the HC, both the acute and chronic LHON patients had consistently significantly lower fractional anisotropy (FA) and higher radial diffusion (RD) for feeder connections (p < 0.05, FDR correction). Acute LHON patients had significantly lower FA and higher RD for local connections (p < 0.05, FDR correction). There was no significant difference in large-scale brain structural connectivity between acute and chronic LHON (p > 0.05, FDR correction). NBS also identified reduced FA of three feeder connections and five local ones linking visual, auditory, and basal ganglia areas in LHON patients (p < 0.05, FDR correction). No structural connections showed linear or nonlinear association with either disease duration or neuro-ophthalmological indicators (p > 0.05, FDR correction). A significant negative correlation was shown between the retinal nerve fiber layer (RNFL) thickness and disease duration (p < 0.05, FDR correction). Conclusions Abnormal rich club organization of the structural network was identified in both the acute and chronic LHON. Furthermore, our findings suggest the coexistence of both primary and secondary connectivity damage in the LHON.

BACKGROUND AND PURPOSE:Leber hereditary optic neuropathy (LHON) is a disease maternally inherited from mitochondria that predominantly impairs the retinal ganglion cells and their axons. To identify whether occult brain white matter (WM) impairment is involved, a voxel-based analysis (VBA) of diffusion metrics was carried out in LHON patients with normal-appearing brain parenchyma. METHODS:Fifty-four symptomatic LHON patients (including 22 acute LHON with vision loss for ≤12 months, and 32 chronic LHON) without any visible brain lesions and 36 healthy controls (HCs) were enrolled in this study. VBA was applied to quantify the WM microstructural changes of LHON patients. Finally, the associations of the severity of WM impairment with disease duration and ophthalmologic deficits were assessed. RESULTS:Compared with the HCs, the average retinal nerve fiber layer (RNFL) thickness was significantly reduced in patients with chronic LHON, whereas it was increased in patients with acute LHON (p < 0.05, corrected). VBA identified significantly decreased fractional anisotropy widely in WM in both the acute and chronic LHON patients, including the left anterior thalamic radiation and superior longitudinal fasciculus, and bilateral corticospinal tract, dentate nuclei, inferior longitudinal fasciculus, forceps major, and optic radiation (OR; p < 0.05, corrected). The integrity of most WM structures (except for the OR) was correlated with neither disease duration nor RNFL thickness (p > 0.05, corrected). CONCLUSIONS:Occult primary impairment of widespread brain WM is present in LHON patients. The coexisting primary and secondary WM impairment may jointly contribute to the pathological process of LHON.

ObjectiveSubclinical abnormalities, including microangiopathy, swelling of nerve fibers, visual field abnormalities and visual functional impairments had been reported in Leber's hereditary optic neuropathy (LHON) carriers. The purpose of this study was to investigate microstructural changes of brain white matter in asymptomatic LHON carriers using DTI and tract-based spatial statistics (TBSS).MethodsDTI and neuro-ophthalmologic measurements were acquired in 14 LHON carriers and 15 gender- and age-matched healthy controls, and diffusion metrics, including fractional anisotropy (FA), axial (AD), radial diffusion (RD) and mean diffusion (MD) were calculated. Intergroup differences in diffusion metrics were compared regressing out potential nuisance covariates of age and gender. A correlation analysis was performed to test associations between abnormal neuro-ophthalmologic measures and diffusion metrics while controlling the effects of age and gender.ResultsCompared to healthy controls, LHON carriers showed a weak increase of thickness of the retinal nerve fiber layer (RNFL) of the right inferior quadrant (F=5.22, p=0.032, before multiple comparison correction). LHON carriers exhibited widespread decreased FA value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, major and minor forceps, bilateral inferior fronto-occipital fasciculi and left superior longitudinal fasciculus), increased RD value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, major and minor forceps, bilateral inferior fronto-occipital fasciculi, bilateral inferior longitudinal fasciculi, bilateral superior longitudinal fasciculi and bilateral uncinate fasciculi) and increased MD value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, minor forceps, bilateral inferior fronto-occipital fasciculi, bilateral inferior longitudinal fasciculi, left superior longitudinal fasciculus and bilateral uncinate fasciculi). Moreover, these changed diffusion metrics were not correlated with age, gender, LHON mutations and retinal measures in LHON carriers.ConclusionOur results show microstructural alterations in brain white matter in asymptomatic LHON carriers, indicating that LHON-related genetic mutations themselves might result in occult white matter alterations in the brain.

PURPOSE:To quantitatively analyze the optic nerve alterations in chronic Leber's hereditary optic neuropathy (LHON) using reduced field-of-view diffusion tensor imaging (rFOV-DTI) and evaluate the correlation of diffusion parameters with visual functional and peripapillary retinal nerve fiber layer (RNFL) thickness. METHODS:Twenty-five patients (50 affected optic nerves) with chronic LHON and 28 healthy controls (56 normal optic nerves) were enrolled. The rFOV-DTI was performed in the bilateral optic nerves for all the subjects. The fractional anisotropy (FA), mean diffusivity (MD), principal eigenvalue (λ//), and orthogonal eigenvalue (λ⊥) were calculated for quantitative analysis. Visual field (VF) and visual acuity (VA) were measured in all subjects. The peripapillary RNFL thickness was assessed using optical coherence tomography (OCT). The correlation of DTI diffusion parameters with visual function and peripapillary RNFL thickness was evaluated. RESULTS:Compared with optic nerves in the control group, the mean FA was significant decreased (P<0.005), and the mean MD, λ//and λ⊥ significant increased (P<0.005). The average and temporal peripapillary RNFL thickness were significantly thinned in LHON patients. There was a significant correlation between optic nerve FA and VA, mean deviation of visual field (MDVF) (P<0.005). Also, optic nerve FA correlated significantly with average RNFL thickness (P<0.05) but not with MD, λ//and λ⊥ (P>0.05). However, none of the DTI parameters correlated with age and disease duration (P>0.05). CONCLUSIONS:Our study has demonstrated that rFOV-DTI could provide information of optic nerve damage in chronic LHON, and can serve as technique for detecting and evaluating pathological changes in the optic nerve in LHON.

Objective To observe quantitatively the optic radiation alterations in chronic Leber's hereditary optic neuropathy (LHON) using MR diffusion tensor imaging at 3.0 T.Methods Twenty-five patients with chronic LHON and twenty-eight sex-and age-matched disease-free control subjects wereenrolled from March 2011 to December 2014.The whole brain DTI examination and retinal opticalcoherence tomography were performed in all the subjects.The parameters values of optic radiation includingfractional anisotropy(FA),mean diffusivity(MD),principal eigenvalue(λ//),orthogonal eigenvalue(λ⊥) and average retinal nerve fiber layer (RNFL) thickness and temporal retinal nerve fiber layer(RNFL) thickness were measured.For DTI and OCT parameters,differences between patients and controls and differences right and left of the patient group were evaluated using independent-samples t test and paired t test respectively.Results In LHON patients,the DEC maps showed that the bilateral optic radiation fibers were obviously sparse and slender.The values of FA,MD,λ// and λ⊥ in the right optic radiation were 0.523±0.050,(0.903±0.061) × 10-9 mm2/s,(4.999 ±-0.097) × 10-9 mm2/s and (4.126-± 0.065) × 10-9 mm2/s respectively,and the corresponding values of left optic radiation were 0.537±0.041,(1.057±0.573)× 10-9 mm2/s,(5.052±0.119)×10-9 mm2/s and (4.138±0.072)×1009 mm2/s.Compared with optic radiation in the control group,the bilateral FA was significant reduced,the bilateral λ⊥ value and right MD value were significant increased (t=-6.524,-6.045,6.932,6.454,3.471,P＜0.05).However,there were no significant difference of the bilateral λ〃 and left MD (t=-0.457,1.221,1.833,P＞0.05).There were no significant differences in FA,MD,λ//and λ⊥ between the left and right eyes in LHON patients(P＞0.05).The values of average RNFL thickness and temporal RNFL thickness in right eyes were (59.36± 10.94) and (41.72±9.43) μm respectively,and the corresponding values of left eyes were (60.12±9.81),(44.72±9.43) μm.The average and temporal RNFL thickness were significantly thinned in LHON patients compared with the control group(t=-16.357,-10.398,-17.169,-9.672,P＜0.05).There was no significant difference in average RNFL thickness between the left and right eyes (t=0.959,P＞0.05),temporal RNFL thickness between the left and right eyes was statistically significant (t=2.645,P＜0.05).Conclusion The bilateral optic radiation had significant degeneration and atrophy in chronic LHON.

Objective To assess the anatomic morphology of the connective structures among brain ventricles and cerebrospinal fluid (CSF) movement in them by CSF spin-labeling MR imaging. Methods According to the order of registration, 50 healthy volunteers were randomly selected and received cerebrospinal fluid spin-labeling MR scan with time-spatial labeling inversion recovery single-shot fast spin echo sequence (SLIR-SSFSE). The tagged CSF was used as an endogenous tracer. The anatomic morphology of the connective structures of brain ventricles and the flow direction of CSF were observed. The longitudinal diameter and transverse diameter of bilateral foramina of monro, midbrain aqueduct, and the central and bilateral lateral apertures of the fourth ventricle of each subject were measured and calculated based on multiple measurements. The flow rate of CSF was calculated based on the flow distance of CSF in the connective structures between brain ventricles during different TI time. The mean value of each indicator was acquired. Results Two-way flow state of CSF was observed in all connective structures, including bilateral foramina of monro, midbrain aqueduct, and the central and bilateral lateral apertures of the fourth ventricle. On the coronal planes, foramen of monro appears as a "Y"-type tubular structure locating among the both sides of the anteriomedial thalamus and fornix, which connect upward with bilateral lateral ventricles and downward with the third ventricle. The longitudinal diameter and transverse diameter of the left side of foramen of monro were 3.50-5.50 mm[mean (4.37 ±0.47)mm]and 1.00-1.40 mm[mean(1.21 ±0. 13) mm], respectively. The longitudinal diameter and transverse diameter of the right side of foramen of monro were 4. 20-4. 80 mm[mean(4.42 ± 0.20) mm]and 1.00-1.60 mm[mean (1.21 ±0. 19) mm], respectively. On the sagittal planes, foramen of monro appeared as an oblique fine tubular structure with the angle of 55°-58° between the both sides. CSF flow velocity towards the foot was 1.61-2. 52 mm/s[mean (2. 00 ± 0. 17) mm/s]in the left side of foramen of monro and 1.93-2. 20 mm/s [mean (2.03 ±0.09) mm/s]in the right side of foramen of monro. On the sagittal planes, midbrain aqueduct appeared as a curved tubular structure through diencephalon, with the longitudinal diameter of 9.90-17.30 mm[mean(15.51 ± 1.70) mm]and the transverse diameter of 1.70-2.30 mm[mean (1.92 ± 0. 17)mm]. In midbrain aqueduct, CSF flow velocity towards the foot was about 5.00-8.74 mm/s[mean (7.84 ±0.86) mm/s]and towards the head was about 3.84-6.71 mm/s[mean (6. 01 ±0. 66) mm/s]. On the sagittal plane, the central apertures of the fourth ventricle appeared as a fork-like tubular structure, with a small bifurcation forward to the central canal of the medulla oblongata and a posterior branch downward to cerebellomedullary cistern. On the coronal plane, lateral apertures of the fourth ventricle appeaed as curved tubular structures connecting the lateral horn of the fourth ventricle and cerebellomedullary cistern. The longitudinal diameter and transverse diameter of the left lateral aperture were 6.30-14. 60 mm[mean (10.42 ±2.88) mm]and 1.00-1.50 mm[mean (1.24 ±0.18) mm],respectively; of the right lateral aperture, they were 6. 20-15.50 mm[mean (12. 13 ± 3.05) mm]and 1.00-1.40 mm[mean(1.19 ±0. 13) mm], respectively. The angle range between the left and right lateral aperture was from 87° to 114°. CSF flow velocity towards the foot was about 2. 89-6. 70 mm/s[mean (4. 78 ± 1.32) mm/s]in the left lateral aperture and 2. 84-7.11 mm/s[mean (5.56 ±1.40) mm/s]in the right lateral aperture. Conclusions CSF spin-labeling MR imaging could display the anatomic morphology of the connective structure among brain ventricles and could be used for noninvasively assessing CSF movement.