Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

SOX17 is expressed in regenerating oligodendrocytes in experimental models of demyelination and in multiple sclerosis.

We have previously demonstrated that Sox17 expression is prominent at developmental stages corresponding to oligodendrocyte progenitor cell (OPC) cycle exit and onset of differentiation, and that Sox17 promotes initiation of OPC differentiation. In this study, we examined Sox17 expression and regulation under pathological conditions, particularly in two animal models of demyelination/remyelination and in post-mortem multiple sclerosis (MS) brain lesions. We found that the number of Sox17 expressing cells was significantly increased in lysolecithin (LPC)-induced lesions of the mouse spinal cord between 7 and 30 days post-injection, as compared with controls. Sox17 immunoreactivity was predominantly detected in Olig2(+) and CC1(+) oligodendrocytes and rarely in NG2(+) OPCs. The highest density of Sox17(+) oligodendrocytes was observed at 2 weeks after LPC injection, coinciding with OPC differentiation. Consistent with these findings, in cuprizone-treated mice, Sox17 expression was highest in newly generated and in maturing CC1(+) oligodendrocytes, but low in NG2(+) OPCs during the demyelination and remyelination phases. In MS tissue, Sox17 was primarily detected in actively demyelinating lesions and periplaque white matter. Sox17 immunoreactivity was co-localized with NOGO-A+ post-mitotic oligodendrocytes both in active MS lesions and periplaque white matter. Taken together, our data: (i) demonstrate that Sox17 expression is highest in newly generated oligodendrocytes under pathological conditions and could be used as a marker of oligodendrocyte regeneration, and (ii) are suggestive of Sox17 playing a critical role in oligodendrocyte differentiation and lesion repair.

Atomic structure of Mn wires on Si(001) resolved by scanning tunneling microscopy.

At submonolayer coverage, Mn forms atomic wires on the Si(001) surface oriented perpendicular to the underlying Si dimer rows. While many other elements form symmetric dimer wires at room temperature, we show that Mn wires have an asymmetric appearance and pin the Si dimers nearby. We find that an atomic configuration with a Mn trimer unit cell can explain these observations as due to the interplay between the Si dimer buckling phase near the wire and the orientation of the Mn trimer. We study the resulting four wire configurations in detail using high-resolution scanning tunneling microscopy (STM) imaging and compare our findings with the STM images simulated by density functional theory.

Cortical demyelination in PML and MS: Similarities and differences.

OBJECTIVE: To characterize pathologic changes in the cerebral cortex of patients with multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML). METHODS: Autopsy brain tissue was obtained from 13 patients with PML, 4 patients with MS, 2 patients with HIV encephalopathy, and 1 subject without neurologic pathology. Immunohistochemistry for myelin proteins, inflammatory cells, and neurofilaments was performed to evaluate the distribution of cortical lesions, their inflammatory activity, and neuritic pathology. Confocal microscopy was applied to examine pathologic changes in neurites in PML cortex. RESULTS: Leukocortical, intracortical, and subpial patterns of cortical demyelination were represented in MS brain tissue. In PML brain tissue intracortical and leukocortical but not subpial lesions were observed. Cortical lesions in PML and MS contained fewer inflammatory cells than demyelinated areas in the white matter. Neuritic pathology in cortical PML lesions was represented by dystrophic and transected neurites. Pathologic modifications in neuritic processes in PML were more evident in highly inflamed white matter than in gray matter areas of demyelination, reminiscent of previous reports of neuritic pathology in MS. JC virus-infected cells were associated with PML white matter, leukocortical and intracortical lesions. CONCLUSIONS: Cortical pathology represents a distinct feature of progressive multifocal leukoencephalopathy. Similarities and differences with regard to multiple sclerosis cortical pathology were noted and may be informative regarding the pathogenesis of both disorders.

Determination of ascorbic acid in beers by high-performance liquid chromatography with electrochemical detection.

A reversed-phase high-performance liquid chromatographic method with electrochemical detection was developed for the determination of ascorbic acid in beers at the nanogram level. The column was packed with C18 bonded silica, commercially available or prepared in the laboratory. The eluent was a citrate buffer solution with an ion-pairing reagent. Several fatty amines were tested as such reagents. Good recoveries indicated that no interfering substances were eluted together with ascorbic acid. The main advantages are the rapid and simple preparation of the samples and the specificity and sensitivity of the detector, which are superior to those of any other detection systems proposed for the determination of ascorbic acid in beers.

Thermooptic coupler for multimode optical fibers.

The detailed theory is presented together with design considerations and recent experimental results for an electronically controllable directional coupler for multimode optical fibers. The device, based on plastic-clad silica fiber, is of exceptionally simple construction and compact size and is highly reliable. A theoretical model of the coupler is described and compared with actual device performance. The coupling can be varied from -4 to -28 dB with an excess loss of <0.2 dB over the entire coupling range, in agreement with theory. Improvements in the present device design are also discussed.