Whole-Brain Diffusion Tensor Imaging in Correlation to Visual-Evoked Potentials in Multiple Sclerosis: A Tract-Based Spatial Statistics Analysis

BACKGROUND AND PURPOSE:Functional correlates of microstructural damage of the brain affected by MS are incompletely understood. The purpose of this study was to evaluate correlations of visual-evoked potentials with microstructural brain changes as determined by DTI in patients with demyelinating central nervous disease.MATERIALS AND METHODS:Sixty-one patients with clinically isolated syndrome or MS were prospectively recruited. The mean P100 visual-evoked potential latencies of the right and left eyes of each patient were calculated and used for the analysis. For DTI acquisition, a single-shot echo-planar imaging pulse sequence with 80 diffusion directions was performed at 3T. Fractional anisotropy, radial diffusivity, and axial diffusivity were calculated and correlated with mean P100 visual-evoked potentials by tract-based spatial statistics.RESULTS:Significant negative correlations between mean P100 visual-evoked potentials and fractional anisotropy and significant positive correlations between mean P100 visual-evoked potentials and radial diffusivity were found widespread over the whole brain. The highest significance was found in the optic radiation, frontoparietal white matter, and corpus callosum. Significant positive correlations between mean P100 visual-evoked potentials and axial diffusivity were less widespread, notably sparing the optic radiation.CONCLUSIONS:Microstructural changes of the whole brain correlated significantly with mean P100 visual-evoked potentials. The distribution of the correlations showed clear differences among axial diffusivity, fractional anisotropy, and radial diffusivity, notably in the optic radiation. This finding suggests a stronger correlation of mean P100 visual-evoked potentials to demyelination than to axonal damage.

MR imaging plays a pivotal role in establishing the diagnosis and follow-up of MS.^1,2 Besides conventional MR imaging, an advanced technique frequently used in MS studies is DTI.³ By measuring the diffusion directions of water molecules, DTI is capable of detecting microstructural changes not visible on standard MR imaging. Common parameters obtained from DTI to assess these changes are fractional anisotropy (FA) and mean diffusivity. Recently, mean diffusivity was further analyzed and divided into radial diffusivity (RD) and axial diffusivity (AD), parameters that allow a more specific approach to the underlying microstructural changes.^4,5 AD was shown to be the primary correlate for histologic markers of axonal integrity,⁴ while RD was suggested to provide a specific tool to assess demyelination, distinct from axonal damage.⁵Pattern reversal visual-evoked potentials (VEP) are an established tool for the evaluation of the optic pathway within the diagnostic work-up of MS, especially as a marker of the integrity of the prechiasmal part.^6–8 However, they failed to provide reliable results in predicting lesions of the retrochiasmal part.^9,10 Evoked potentials, in general, and combined evoked potential analysis, in particular, seem to correlate well with the long-term disability of patients with MS. Correlations of evoked potentials and MR imaging are reported controversially. While some studies showed no correlations between evoked potentials and MR imaging,¹¹ other studies reported significant correlations between VEP and T2 lesion load.¹² However, to the best of our knowledge, a correlation of DTI with VEP has not been published.The aim of our study was, therefore, to evaluate the correlation of VEP with parameters derived from DTI with the following objectives: 1) to identify potential relations of VEP to microstructural changes, and 2) to analyze whether such changes reflect demyelination or axonal damage.     

An Indentation Technique to Characterize the Mechanical and Viscoelastic Properties of Human and Porcine Corneas

Cornea is a load-bearing tissue whose mechanical and viscoelastic characteristics are not well understood, due to the challenge associated with most of the measurements. A novel indentation technique has been developed for mechanical characterization of human and porcine corneal tissue, using a tailored depth-sensing microindentation instrument. During indentation, the corneas were suspended by clamping the edges of the cornea, thus allowing depth-sensing measurement free from the complication of the backing substrate. The deformation displacement and the amount of force applied by the indenter were used to obtain hysteresis and stress relaxation data for both human and porcine corneas. Optical coherence tomography was used to measure the thickness of the cornea. Simple theoretical analyses have been undertaken to explain the loading–unloading and the stress relaxation data. The effect of swelling on the mechanical properties of the cornea was also examined. Porcine corneas appeared to be less stiff and to demonstrate more linear response than human corneas under loading. More importantly, it is shown that swelling reduced the strength of the corneas. Our results demonstrate that this new indentation system can be used to characterize the mechanical and viscoelastic properties of corneas.     

First human experience with endoscopically delivered and retrieved duodenal-jejunal bypass sleeve

BACKGROUND: We report the first human experience with an endoscopic duodenal-jejunal bypass sleeve (DJBS) in a community hospital. METHODS: The DJBS is a 60-cm sleeve anchored in the duodenum to create a duodenal-jejunal bypass. In a 12-patient prospective, open-label, single-center, 12-week study, the device was endoscopically implanted, left in situ, and retrieved. The study included 5 men and 7 women, with a mean body mass index of 43 kg/m(2). Of the 12 patients, 4 had type 2 diabetes. The primary endpoints were the incidence and severity of adverse events. The secondary outcomes included the percentage of excess weight loss and changes in co-morbid status. RESULTS: The DJBS was endoscopically delivered and retrieved in all patients (mean implant/explant time of 26.6 and 43.3 min, respectively). Of the 12 patients, 10 were able to maintain the device for 12 weeks and 2 underwent explantation after 9 days secondary to poor device placement. Several self-limited adverse events were possibly or definitely related to the device, including 6 episodes of abdominal pain, 18 of nausea, and 16 of vomiting, mainly within 2 weeks of implantation. Two partial pharyngeal tears occurred during explantation. Implant site inflammation was encountered in all patients. No device-related event was considered severe. The average percentage of excess weight loss for the 10 patients with the device in place for 12 weeks was 23.6%, with all patients achieving at least 10% excess weight loss. All 4 diabetic patients had normal fasting plasma glucose levels without hypoglycemic medication for the entire 12 weeks. Of these 4 patients, 3 had decreased hemoglobin A(1c) of > or =.5% by week 12. CONCLUSION: The DJBS can be safely delivered and removed endoscopically and left in situ for 12 weeks. The device had a favorable safety and encouraging efficacy profile. Randomized prospective trials are warranted.     

Acute and chronic neuroendocrine effects of interferon-beta 1a in multiple sclerosis

OBJECTIVE: Treatment of multiple sclerosis with interferon-beta (IFN-beta) results in variable responses interindividually. Cytokine-hormone interactions may modulate the therapeutic effects of IFN-beta. Since hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis and other neuroendorine disturbances occur in multiple sclerosis, we determined the detailed neuroendocrine response of patients with multiple sclerosis to IFN-beta. DESIGN: Longitudinal open-label study. PATIENTS: Eight patients with relapsing-remitting multiple sclerosis (four women, age 31.9 +/- 1.5 years, EDSS 1.5-2.5). MEASUREMENTS: Plasma ACTH, cortisol, prolactin, GH, TSH, LH and FSH were determined in 30-min intervals during 8 h on four occasions: after intramuscular injection of saline; after the first dose of IFN-beta 1a; after the second IFN-beta dose with oral indomethacin pretreatment; and after 3 months of IFN-beta therapy. Dexamethasone-corticotropin-releasing hormone test was performed before and at 3 months on IFN-beta. RESULTS: Compared to saline, IFN injection resulted in marked rise in plasma ACTH (mean, 370% of baseline), cortisol (214%), prolactin (253%) and GH (756%), between 2 and 6 h after injection. With indomethacin, hormone secretion occurred with reduced peak values. Endocrine response adapted partially after 3 months of treatment. HPA axis activity decreased in most patients, but increased in one patient with frequent relapses. CONCLUSIONS: Marked neuroendocrine effects occur in response to IFN-beta in multiple sclerosis. Upon prolonged treatment, these effects partially adapt, and HPA axis hyperactivity is reduced. Prospective studies to determine the relation to individual treatment response can be based on these findings.     

Cardiovascular Risk and Statin Eligibility of Young Adults After an MI: Partners YOUNG-MI Registry

Background

Despite significant progress in primary prevention, the rate of MI has not declined in young adults.

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and colorectal neoplasia tissues from Puerto Ricans.METHODS:Tissues from patients with IBD,colitisassociated colorectal cancer(CAC),sporadic dysplasia,and sporadic colorectal cancer(CRC),as well as normal controls,were identified at several centers in Puerto Rico.Archival formalin-fixed,paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R,p EGFR,Cox-2,and VDR.Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a4-point scale that assessed intensity of staining.Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia,in addition to the areas of cancer,within each tissue.Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test.The mean scores for normal tissues and tissues with IBD,dysplasia,CRC,and CAC were calculatedand statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test.Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient.Data are presented as mean±SE.RESULTS:On average,patients with IBD were younger(34.60±5.81)than normal(63.20±6.13,P0.01),sporadic dysplasia(68.80±4.42,P0.01),sporadic cancer(74.80±4.91,P0.001),and CAC(57.50±5.11,P0.05)patients.NK-1R in cancer tissue(sporadic CRC,1.73±0.34;CAC,1.57±0.53)and sporadic dysplasia(2.00±0.45)were higher than in normal tissues(0.73±0.19).p EGFR was significantly increased in sporadic CRC(1.53±0.43)and CAC(2.25±0.47)when compared to normal tissue(0.07±0.25,P0.05,P0.001,respectively).Cox-2 was significantly increased in sporadic colorectal cancer(2.20±0.23 vs 0.80±0.37 for normal tissues,P0.05).In comparison to normal(2.80±0.13)and CAC(2.50±0.33)tissues,VDR was significantly decreased in sporadic dysplasia(0.00±0.00,P0.001 vs normal,P0.001 vs CAC)and sporadic CRC(0.47±0.23,P0.001 vs normal,P0.001 vs CAC).VDR levels negatively correlated with NK-1R(r=-0.48)and p EGFR(r=-0.56)in normal,IBD,sporadic dysplasia and sporadic CRC tissue,but not in CAC.CONCLUSION:Immunohistochemical NK-1R and p EGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia.VDR immunoreactivity can distinguish CAC from sporadic cancer.     

自体松质骨支持引导组织再生膜重建牙槽嵴的初步临床研究

目的:观察自体松质骨结合引导组织再生膜技术重建牙槽嵴的临床效果。方法:小切口微创取自体髂骨松质骨粒移植于牙槽嵴表面,上方覆盖聚四氟乙烯引导膜,为6例患者修复萎缩或缺损的牙槽嵴,分别在术前,术后1周,12周进行临床检查、测量重建高度或宽度,作X线检查,并对1例患者12周时的再生骨行组织学检查,观察临床重建效果。结果:牙槽嵴形态以及骨量较手术前得到明显改善,12周时6例牙槽嵴平均增宽,增高4.20 mm,X线检查表明术后植骨区骨组织量增多、骨密度较术前更致密;术后12周植骨部位组织学表现为排列不规则的板层新生骨,可见大量的成骨细胞突起。结论:自体松质骨移植与膜引导组织骨再生技术联合增高牙槽嵴取得满意疗效,值得推广应用。