Abnormal corpus callosum induced by overt hepatic encephalopathy impairs interhemispheric functional coordination in cirrhosis patients.

BACKGROUND: Although overt hepatic encephalopathy (OHE) patients were shown to have bilaterally symmetrical structural and functional abnormalities in the whole brain, few studies have focused on the bilateral cerebral hemisphere commissural fibers and measured functional coordination between bilateral hemispheres. This study aimed to investigate the structural changes of the corpus callosum (CC) and interhemispheric functional coordination in patients with OHE and to test the hypothesis that abnormal CC induced by OHE impairs interhemispheric functional coordination in cirrhosis patients. METHODS: The microstructural integrity and the volumes of each subregion of the CC were analyzed by diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging. Voxel-mirrored homotopic connectivity (VMHC) was derived from resting-state functional magnetic resonance imaging (MRI). RESULTS: Compared with the healthy controls (HCs) and patients without hepatic encephalopathy (noHE), the OHE group showed decreased volumes in all subregions of the CC. In OHE patients, the decreased fractional anisotropy (FA) of CC-5 correlated with decreased VMHC in the middle occipital gyrus (MOG) and precuneus. The value of FA in CC-5 and the volumes of CC-3, CC-4, and CC-5 showed correlations with neuropsychological performance in patients with OHE. CONCLUSIONS: These findings suggest that impairment of interhemispheric white matter pathways may disturb the functional connectivity associated with coordination and neurocognitive performance.

Significant reduction in hemarthrosis in boys with severe hemophilia A: The China hemophilia individualized low-dose secondary prophylaxis study.

INTRODUCTION: In countries with restricted access to clotting factor concentrates, early implementation of low-dose prophylaxis is recommended over episodic treatment. OBJECTIVE: The objective of this 1-year prospective secondary prophylaxis study was to evaluate the efficacy of a dose/frequency escalating protocol in young boys with hemophilia A in China. METHODS: Boys were started on a low-dose protocol (minimum 10-15 IU/kg of factor VIII [FVIII] twice weekly). Escalation was based on index joint bleeding, swelling/persistent joint swelling, and serial ultrasound (gray scale and color Doppler) examinations of index joints. RESULTS: Thirty-three boys, median age 4.8 years (interquartile range, 3.8-6.1) were enrolled in a 3-month observation period that preceded a 1-year prophylaxis phase. A significant reduction in total bleeding events (43.0%, P = .001), index joint bleeds (53.2%, P = .002), and target index joint bleeds (70.0%, P = 0.02) was observed during the prophylaxis phase. During the prophylaxis period, 40% of target joints resolved. The percentage of boys with zero index joint bleeds increased significantly (P = .004) from 51.5% during the observation phase to 81.8% in last quarter of the prophylaxis phase (months 10-12). There was no progression of arthropathy based on physical examination (Hemophilia Joint Health Score), X-ray, and ultrasound obtained at entry into the prophylaxis phase and at study exit. The median FVIII consumption over the prophylaxis phase was 1786 IU/kg/y. CONCLUSION: A low-dose, individualized prophylaxis protocol, guided by individual bleeding profiles and serial assessment of joint status, enables escalation of treatment intensity in boys with severe hemophilia A, leading to a significant reduction in bleeding events and reduction in target joint bleeding.