To determine the relation between baseline MRI and both conversion to multiple sclerosis (MS) and development of disability in a cohort of patients with clinically isolated syndromes (CIS).
From 1995 ...to 1998, 175 consecutive patients with CIS underwent brain MRI within 3 months of their first attack and again 12 months and 5 years later. We studied the number and location of lesions at baseline and development of new T2 lesions. We also analyzed conversion to MS and development of disability (Expanded Disability Status Scale EDSS > or = 3.0).
We included 156 patients with CIS followed for a median of 7 years. Compared to the reference group with 0 Barkhof criteria at baseline MRI, patients with one or two Barkhof criteria showed an adjusted hazard ratio (HR) of 6.1 (2.2 to 16.6) and patients with three to four Barkhof criteria of 17.0 (6.7 to 43) for conversion to MS and differentiated patients with low, medium, and high conversion risk. EDSS at year 5 correlated with baseline number of Barkhof criteria (r = 0.46, p < 0.0001). When categorizing by number of baseline lesions, similar results were seen. Patients with a baseline MRI with three to four Barkhof criteria had an adjusted HR of 3.9 (1.1 to 13.6) for reaching EDSS > or = 3.0. Only 10% of the latter had disability at year 5, but 40% reached this at 8 years.
Baseline MRI determines the risk for converting to clinically definite multiple sclerosis and correlates with disability at 5 years. The proportion of patients developing disability is low during the first 5 years but rapidly increases shortly after.
Background and purpose
Both optical coherence tomography (OCT) and magnetic resonance imaging (MRI) volumetric measures have been postulated as potential biomarkers of multiple sclerosis (MS)‐related ...disability. The aim of the study was to investigate the association between OCT and brain volume and spinal cord area (SCA) parameters in patients with relapsing MS and to assess their independent associations with disability.
Methods
This was a cross‐sectional analysis of 90 patients with MS who underwent OCT and MRI examination. Values of peripapillary retinal nerve fibre layer (pRNFL), ganglion cell/inner plexiform layer (GCIPL) and inner nuclear layer of eyes without previous optic neuritis were obtained. SCA and brain parenchymal fraction (BPF), grey and white matter fractions were obtained. Multivariable regression analyses were conducted with disability as dependent variable.
Results
Lower pRNFL thickness and lower GCIPL volume as well as lower BPF, grey matter fraction and SCA were associated with a longer disease duration and a higher Expanded Disability Status Scale score. Lower pRNFL thickness and GCIPL volumes were associated with lower BPF and SCA. In the multivariable logistic regression analyses, pRNFL thickness and GCIPL volume outperformed MRI in predicting disability.
Conclusions
The OCT measures correlate with brain and spinal cord atrophy and appear more closely associated with disability than MRI volumetric measures.
In recent years, criteria for the diagnosis of multiple sclerosis (MS) have changed, mainly due to the incorporation of new MRI criteria. While the new criteria are a logical step forward, they are ...complex and-not surprisingly-a good working knowledge of them is not always evident among neurologists and neuroradiologists. In some circumstances, several MRI examinations are needed to achieve an accurate and prompt diagnosis. This provides an incentive for continued efforts to refine the incorporation of MRI-derived information into the diagnostic workup of patients presenting with a clinically isolated syndrome. Within the European multicenter collaborative research network that studies MRI in MS (MAGNIMS), a workshop was held in London in November 2007 to review information that may simplify the existing MS diagnostic criteria, while maintaining a high specificity that is essential to minimize false positive diagnoses. New data that are now published were reviewed and discussed and together with a new proposal are integrated in this position paper.
Inflammation and neurodegeneration may have differential impacts on disease evolution in the different forms of multiple sclerosis. However, a beneficial effect of immunomodulatory drugs should not ...be ruled out in primary progressive multiple sclerosis. Our aim is to investigate the safety and efficacy of interferon beta-1b in primary progressive multiple sclerosis. We conducted a double-blind, stratified, randomized, parallel group, phase II pilot study where patients with primary progressive multiple sclerosis or ‘transitional’ forms of multiple sclerosis received interferon beta-1b at doses of 8 MIU or placebo for 24 months. The main objective of the study was to investigate the safety and tolerability of interferon beta-1b. The primary efficacy variable was the time to neurological deterioration (Expanded Disability Status Scale) confirmed at 3 months. Seventy-three patients were included and three dropped out the study. More patients in the treatment arm had at least one related adverse event (94.4% versus 45.9%; p < 0.001); no other significant differences in safety endpoints were observed. Time to neurological deterioration was not different between trial arms (log-rank test, p = 0.3135). Statistically significant differences favoring treatment were observed for the Multiple Sclerosis Functional Composite score at several timepoints, T1 and T2 lesion volume changes at 12 and 24 months, mean number of active lesions and proportion of patients with active lesions at 24 months. We conclude that interferon beta-1b is safe and well tolerated in patients with primary progressive multiple sclerosis and transitional multiple sclerosis. Positive effects of interferon beta on secondary clinical and magnetic resonance imaging outcomes were observed, but a beneficial effect on Expanded Disability Status Scale progression was not demonstrated.
The Abel inversion method is the classic approach to retrieve electron density profiles from radio occultation measurements, assuming that the electron density is only dependent upon height. In the ...early 2000s, the total electron content (TEC)‐aided inversion method was introduced, where horizontal gradients in the electron density distribution are taken into account by using information from an external model of total electron content (TEC). We show how the quality of the chosen external ionospheric model influences the radio occultation retrievals. Using a two‐layer TEC model, the 68% percentiles of the global error distributions of retrieved critical frequency and bottomside ionospheric electron content for 2014 improve more than 30%, with regard to the classic Abel inversion results. In a well‐sounded region like Europe, this improvement raises to about 40–45%, while 10% improvement is achieved using two‐layer maps with regard to the retrievals using single‐layer TEC maps. We point out that using the TEC to describe the horizontal gradient incurs an implicit mismodeling that, until now, has not been taken into account. A new technique is presented that, thanks to TEC modeling by means of two layers, can assess the impacts of such mismodeling. From this technique, a method to select the most accurate radio occultation retrievals is applied to demonstrate that the resulting errors in the retrieved critical frequencies for the European region are smaller than 7% in nearly 82% of the cases, very similar to the relative difference between measurements of two nearby ionosondes.
Key Points
TEC‐aided radio occultation (RO) retrieval of electron density is demonstrated to be more accurate than the classic method assuming spherical symmetry
This accuracy increases with the accuracy of the TEC model used. A method based in two‐layer TEC maps is introduced for selecting the most accurate RO retrievals
Critical frequency RO retrievals aided by two‐layer TEC maps provide similar accuracy as ionosonde measurements in the European region
Background:
Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease.
Objectives:
The Magnetic Imaging in MS ...(MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS.
Methods:
Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups).
Results:
In the binary model, UCCA (p < 0.01) and T2LV (p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA (p < 0.01), T2LV (p = 0.02) and GMF (p = 0.04) were independently associated with disability.
Conclusions:
Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.
Wernicke encephalopathy (WE) is a severe neurologic disorder resulting from dietary vitamin B(1) deficiency. This study was undertaken to analyze and compare MR imaging findings and neurologic ...manifestations at clinical presentations of patients with WE with and without a history of alcohol abuse.
WE patients were identified using diagnostic neurologic data bases. Fifty-six patients (29 females, 27 males) diagnosed between 1999 and 2008 with WE who improved within 1 month from the onset of thiamine administration were included in the analysis. Patients' records were reviewed for clinical manifestations and imaging studies' findings. MR imaging was performed in the acute phase of the disease at a field strength of 1T (16 patients) and 1.5T (40 patients). All MR images were of acceptable to good quality and were retrospectively reviewed. We compared imaging findings and clinical presentation in the alcoholic (AL) group versus the non-alcoholic (NA) group using the 2-tailed Fisher exact test and the Phi coefficient as appropriate.
Forty-three percent of the patients were in the AL group, whereas 57% were in the NA group. Eighty-nine percent showed changes in consciousness, 75% had ocular manifestations, and 54% had ataxia. On MR imaging, 80% of the patients had evidence of symmetric lesions in the medial thalami and in the periventricular region of the third ventricle; 59%, in the periaqueductal area; 45%, in the mamillary bodies; 36%, in the tectal plate; and 7%, in the periventricular gray matter located anteriorly to the fourth ventricle. Signal-intensity alterations in areas considered atypical for the disease were noted only in the NA group and always in association with the typical findings. Contrast enhancement of the thalamus and mamillary bodies was significantly associated with alcohol abuse.
Contrast enhancement in the mamillary bodies and thalamus is a typical finding of the disease in AL patients. Atypical MR imaging findings characterize NA patients.
Denitrifying bioelectrochemical systems (d-BES) are a promising technology for nitrate removal from wastewaters. Microbial community monitoring is required to pave the way to application. In this ...study, for the first time flow cytometry combined with molecular biology techniques is exploited to monitor and determine the structure-function relationship of the microbiome of a denitrifying biocathode. Stable cathode performance at poised potential (-0.32 V vs.Ag/AgCl) was monitored, and different stress-tests were applied (reactor leakage, nitrate concentration, buffer capacity). Stress-tests shifted the reactor microbiome and performance. The monitoring campaign covered a wide range of nitrate consumption rates (from 15 to 157 mg N L sub(NCC) super(-1) d super(-1)), current densities (from 0 to 25 mA L sub(NCC) super(-1)) and denitrification intermediates (nitrite and nitrous oxide consumption rates varied from 0 to 56 mg N L sub(NCC) super(-1) d super(-1)). The reactor microbiome (composed of 21 subcommunities) was characterized and its structure-function relationship was revealed. A key role for Thiobacillussp. in the bioelectrochemical reduction of nitrate was suggested, while a wider number of subcommunities were involved in NO sub(2) super(-) and N sub(2)O reduction. It was demonstrated that different bacteria catalyze each denitrification step in a biocathode. This study contributed significantly to understanding denitrifying biocathodes, paving the way for their knowledge-driven engineering.
Background and objective
Several criteria for treatment response to interferon beta (IFNβ) have been proposed, although there is no consensus among different investigators. Hence, the aim of this ...study was to investigate magnetic resonance imaging (MRI) and clinical predictors of response during the first 12 months of therapy.
Methods
This is a prospective and longitudinal study of relapsing-remitting multiple sclerosis (RRMS) patients treated with IFNβ. Patients were classified based on the presence of new lesions on MRI, relapses, confirmed disability increase, or combinations of all these variables after 1 year of therapy. Regression analysis was performed in order to identify variables of response after a follow-up of 3 years.
Results
We included 222 RRMS patients. The logistic model demonstrated that only the combination of new active lesions on MRI with the presence of relapses (OR 4.4; 95% CI 1.6–12.5) or disability progression (Odds Ratio (OR) 7.1; 95% Confidence Interval (CI) 1.6–33.9), or both (OR 6.5; 95% CI 1.9–23.4) achieved significant values to identify those patients with a poor outcome.
Conclusions
In RRMS patients treated with IFNβ, the combination of measures of disease activity and the presence of new active lesions on MRI may have a prognostic value for identifying patients with disease activity in the second and third year of therapy.
Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly promising novel target in breast cancer. However, the expression of PARP-1 protein in breast cancer and its associations with outcome are yet poorly ...characterized.
Quantitative expression of PARP-1 protein was assayed by a specific immunohistochemical signal intensity scanning assay in a range of normal to malignant breast lesions, including a series of patients (N = 330) with operable breast cancer to correlate with clinicopathological factors and long-term outcome.
PARP-1 was overexpressed in about a third of ductal carcinoma in situ and infiltrating breast carcinomas. PARP-1 protein overexpression was associated to higher tumor grade (P = 0.01), estrogen-negative tumors (P < 0.001) and triple-negative phenotype (P < 0.001). The hazard ratio (HR) for death in patients with PARP-1 overexpressing tumors was 7.24 (95% CI; 3.56–14.75). In a multivariate analysis, PARP-1 overexpression was an independent prognostic factor for both disease-free (HR 10.05; 95% CI 5.42–10.66) and overall survival (HR 1.82; 95% CI 1.32–2.52).
Nuclear PARP-1 is overexpressed during the malignant transformation of the breast, particularly in triple-negative tumors, and independently predicts poor prognosis in operable invasive breast cancer.
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