Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions.

BACKGROUND AND OBJECTIVES: To determine the effects of dimethyl fumarate (DMF) and glatiramer acetate on iron content in chronic active lesions in patients with multiple sclerosis (MS) and in human microglia in vitro. METHODS: This was a retrospective observational study of 34 patients with relapsing-remitting MS and clinically isolated syndrome treated with DMF or glatiramer acetate. Patients had lesions with hyperintense rims on quantitative susceptibility mapping, were treated with DMF or glatiramer acetate (GA), and had a minimum of 2 on-treatment scans. Changes in susceptibility in rim lesions were compared among treatment groups in a linear mixed effects model. In a separate in vitro study, induced pluripotent stem cell-derived human microglia were treated with DMF or GA, and treatment-induced changes in iron content and activation state of microglia were compared. RESULTS: Rim lesions in patients treated with DMF had on average a 2.77-unit reduction in susceptibility per year over rim lesions in patients treated with GA (bootstrapped 95% CI -5.87 to -0.01), holding all other variables constant. Moreover, DMF but not GA reduced inflammatory activation and concomitantly iron content in human microglia in vitro. DISCUSSION: Together, our data indicate that DMF-induced reduction of susceptibility in MS lesions is associated with a decreased activation state in microglial cells. We have demonstrated that a specific disease modifying therapy, DMF, decreases glial activity in chronic active lesions. Susceptibility changes in rim lesions provide an in vivo biomarker for the effect of DMF on microglial activity. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that DMF is superior to GA in the presence of iron as a marker of inflammation as measured by MRI quantitative susceptibility mapping.

Disconnections of Cortico-Subcortical Pathways Related to Cognitive Impairment in Patients with Leukoaraiosis: A Preliminary Diffusion Tensor Imaging Study.

BACKGROUND: We aimed to explore the relation between the microstructural integrity of white matter using the technique of diffusion tensor imaging (DTI) and changes of cognition in leukoaraiosis (LA). METHODS: Fifty patients with LA and 50 age- and gender-matched controls were recruited consecutively. The average values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal-appearing white matter (NAWM) from the regions of interest (ROIs). RESULTS: We found significantly decreased FA and increased MD in WMLs at the 5 ROIs than that in NAWM and controls (p < 0.05). The values of FA in NAWM were significantly lower at centrum semiovale and posterior periventricular white matter than those of controls (p < 0.05). The values of MD in NAWM were significantly higher at the anterior periventricular white matter and corpus callosum than those of controls (p < 0.05). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.420, p = 0.028). CONCLUSIONS: DTI may provide some important information about the cognitive dysfunction in patients with LA, which may largely attribute to the "disconnection" of cortico-subcortical pathways, with the evidence of reduced FA and increased MD.

Correlation between prefrontal-striatal pathway impairment and cognitive impairment in patients with leukoaraiosis.

Our study aimed to investigate the changes of white matter microstructure of cortico-subcortical pathways using diffusion tensor imaging (DTI), and to explore the relationship between abnormal parameters of DTI and cognitive function underlying in patients with leukoaraiosis (LA).A total of 42 patients with LA and 42 age- and sex-matched healthy controls were recruited from Beijing Chaoyang Hospital, Capital Medical University between January 2012 and December 2012. All the subjects underwent scans of conventional magnetic resonance imaging and DTI, and a comprehensive neuropsychological battery was utilized. The regions of interest (ROIs) were located at the white matter of centrum semiovale, anterior and posterior periventricular white matter, basal ganglia, corpus callosum. The averaged values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal appearing white matter (NAWM). A linear regression analysis was performed to assess the association between diffusion parameters and decline in cognitive domains.Patients with LA were associated with comprehensive cognitive function deficits. We found that significantly decreased FA and increased MD in WMLs at the 5 ROIs than that of NAWM and controls (P < .05). The values of FA in NAWM were significantly lower and MD in NAWM were significantly higher at centrum semiovale and posterior periventricular white matter than that of controls (P < .05). The values of FA in WMLs at anterior periventricular white matter were positively related to the performances of cognition in patients with LA (P < .05). The values of FA in NAWM located at anterior periventricular white matter were positively related to the score of Digit-symbol test (r = 0.446, P = .002). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.418, P = .03).In our study, patients with LA exhibited significant cognitive impairment especially in the domains of executive function. The technique of DTI revealed that the reduced FA and increased MD at the corresponding regions of cortico-subcortical pathways in patients with LA. DTI may be of great help for an early pathology of white matter microstructure underlying in patients with LA.

Incidence of pleural effusion in patients with pulmonary embolism.

BACKGROUND: No data on the incidence of pleural effusion (PE) in Chinese patients with pulmonary embolism are available to date. The aim of the current study was to investigate the frequency of PE in a Chinese population of patients with pulmonary embolism. METHODS: This was a retrospective observational single-center study. All data of computed tomography pulmonary angiography (CTPA) performed over 6-year period on adult patients with clinically suspected pulmonary embolism were analyzed. RESULTS: From January 2008 until December 2013, PE was identified in 423 of 3141 patients (13.5%) with clinically suspected pulmonary embolism who underwent CTPA. The incidence of PE in patients with pulmonary embolism (19.9%) was significantly higher than in those without embolism (9.4%) (P < 0.001). Majority of PEs in pulmonary embolism patients were small to moderate and were unilateral. The locations of emboli and the numbers of arteries involved, CT pulmonary obstruction index, and parenchymal abnormalities at CT were not associated with the development of PE. CONCLUSIONS: PEs are present in about one fifth of a Chinese population of patients with pulmonary embolism, which are usually small, unilateral, and unsuitable for diagnostic thoracentesis.

[Multi-slice spiral computed tomography angiography for preoperative evaluation of laparoscopic right hemicolectomy].

OBJECTIVE: To explore the application value of multi-slice spiral CT angiography (MSCTA) for the preoperative evaluation of laparoscopic right hemicolectomy. METHODS: Abdominal CT slice images of 160 patients(group A) were collected for 3-dimensional reconstruction using volume rendering technique. Interpretation and anatomical classification of the major branches and course of the superior mesenteric artery(SMA) in the reconstructed images of the arterial phase were carried out. Forty-five patients(group B) undergoing laparoscopic right hemicolectomy were evaluated with MSCT combining images obtained from the arterial phase and portal venous phase. The relationship between ileocolic artery and ileocolic vein was analyzed. The preoperative imaging findings were compared to that revealed during the procedure. RESULTS: In group A, 70(43.8%) out of 160 patents showed anatomical variations of the superior mesenteric artery, of whom 51(31.9%) had two right colic arteries, and 14(8.8%) had two middle colic arteries. Preoperative MSCTA showed that in group B ileocolic artery was running ventrally to ileocolic vein in 13(28.9%) out of 45 patients, while running dorsally in 32(71.1%). Compared to the skeletonized vessels during the procedure, the consistency rate was 100%. CONCLUSION: Anatomical variations of superior mesenteric artery are common, therefore, multi-slice spiral CT scan is vital for preoperation evaluation.

TRPC6 channel protects retinal ganglion cells in a rat model of retinal ischemia/reperfusion-induced cell death.

PURPOSE: To examine the potential role of transient receptor potential canonical 6 (TRPC6) in the survival of retinal ganglion cells (RGCs) in the rat retinal ischemia/reperfusion (IR) model. METHODS: TRPC6 expression in normal rat retina was analyzed by RT-PCR, Western blot analysis, in situ hybridization, and immunohistochemistry. The rat retinal IR model was established, and then the time course of TRPC6 expression was evaluated. Pharmacologic experiments were conducted. The expression of brain-derived neurotrophic factor (BDNF) was measured in the retinal IR model. Densities of surviving RGCs were estimated by counting fluorogold-labeled cells in 12 standard retinal areas. RESULTS: TRPC6 mRNA and protein are selectively enriched in the RGC layer of the retina. A 60-minute interval of retinal ischemia could induce the elevation of TRPC6 mRNA and protein, both of which peaked 24 hours after reperfusion. TRPC6 protein expression decreased dramatically 1 week later, accompanied by substantial RGC loss. The TRPC channel's agonist significantly increased RGC survival, and the antagonist reduced cell density. The transcription level of the bdnf gene was enhanced at 24 hours; this paralleled the increase of TRPC6. When TRPC6 was blocked, the BDNF precursor (proBDNF), rather than its mature form (mBDNF), increased at 24 hours. CONCLUSIONS: This study documents the pattern of TRPC6 expression in the retinal IR model and provides evidence that activating TRPC channels before ischemia has early neuroprotective effects on RGCs in vivo. The protection of TRPC6 is BDNF mediated, and proBDNF-p75(NTR) signaling may contribute to the death of RGCs in retinal ischemia injury.

The clinical outcomes of three surgical managements on primary angle-closure glaucoma.

PURPOSE: To investigate the efficacy of trabeculectomy, phacotrabeculectomy and phacoemulsification in the management of primary angle closure glaucoma (PACG). METHODS: A prospective observational study was performed in 88 chronic PACG patients (97 eyes) who were divided into three groups following defined indications to receive different surgical interventions. The indications and clinical outcomes were evaluated. The mean follow-up was (17.7 +/- 4.9) months. RESULTS: Success rate in trabeculectomy, phacotrabeculectomy and phacoemulsification group was 81.08%, 78.57% per hundred and 81.25% per hundred, respectively. The anterior chamber depth was deeper and the angle was wider postoperatively vs. preoperatively both in phacotrabeculectomy and phacoemulsification group. No obvious changes were seen in trabeculectomy group. The coefficient of outflow facility of aqueous humor (C values) significantly increased in three groups postoperatively (P < 0.01). No severe intraoperative complications were found and the incidence of postoperative complications was low. Five eyes sustained hypotony 3 +/- 1.87 months in trabeculectomy group and 1 eye happened malignant glaucoma in phacotrabeculectomy group. The visual acuity in patients with phacotrabeculectomy plus intraocular lens implantation and those only with phacoemulsification plus intraocular lens implantation were improved 78.57% and 93.74%, respectively. No significant improvement was found in trabeculectomy group (chi2 = 47.10, P < 0.001). CONCLUSION: Three surgical interventions were beneficial to manage PACG and with co-existing cataract. The indication choosing was suggested according to visual acuity, angle closure circumference, cataract, medication requirements and optic nerve damage. Phacotrabeculectomy was recommended for angle closed > or =180 degrees circumference while phacoemulsification for angle closed <180 degrees.