Glatiramer acetate (GA) is effective in reducing clinical and magnetic resonance imaging (MRI) activity in relapsing-remitting multiple sclerosis (RRMS). Serial long-term MRI data are lacking for ...large cohorts of GA-treated patients. The European/Canadian GA study consisted of two consecutive phases, each lasting nine months. The first treatment phase was randomized, double-blind and placebo-controlled. The second was an open-label, active treatment phase with daily administration of 20 mg GA subcutaneously for all patients. For the long-term follow-up (LTFU), dual echo, pre- and postgadolinium T1-weighted brain MRI scans were obtained with the same acquisition scheme as for the original trial and a neurological assessment was performed. Lesion volumes, normalized brain volumes and percentage brain volume changes (PBVC) were measured. One hundred and forty-two (63.4%) of the 224 patients who completed the two phases of the European/Canadian study underwent the LTFU after a mean period of 5.8 years (range: 5.3-6.4); 73 were treated with GA from study initiation. MRI measures at LTFU did not significantly differ between patients originally assigned to placebo and those who were always treated with GA, but the proportion of patients who did not require walking aids at LTFU was lower in the latter group (P=0.034). PBVC between baseline and LTFU was significantly correlated with lesion load at study entry. An earlier initiation of GA treatment in patients with active RRMS might, at least partially, have a favourable impact on long-term disease evolution. Multiple Sclerosis 2007; 13: 502-508. http://msj.sagepub.com
Background
Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti‐IgE antibody effective in refractory CSU, ...but its mechanism of action and markers predictive of response remain not completely defined.
Objectives
To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d‐dimer (bd‐dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal.
Methods
In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd‐dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2‐ and 3‐month interval after a first and a second course of treatment, respectively.
Results
bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non‐responders (P = 0.0002). Conversely, bd‐dimer did not correlate to response. There was no correlation between both bIgE and d‐dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023).
Conclusions
Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd‐dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk.
Introduction
Multiple sclerosis (MS) is characterized, besides focal lesions, by brain atrophy. The determinants of atrophy rates in individual patients are poorly understood.
Aim
This study ...investigated the predictive value of clinical and magnetic resonance imaging (MRI) factors, including short-term changes thereof, for concurrent and future atrophy evolution using Spearman’s rank correlations and stepwise multiple linear regression.
Methods
We retrospectively identified a group of 115 active, early relapsing-remitting (RR) patients relatively homogeneous in terms of disease course and MRI activity compared to a second group of 96 patients with broader spectrum of MS phenotypes and inactive scans. All patients had undergone three MRI investigations with interscan intervals of at least 12 and 24 months, respectively.
Results
In the RR patients, 23% of variance in concurrent atrophy rates (over the first interval) could be explained by the combination of baseline T2 lesion volume and change in EDSS score over the first interval, whereas only 6% in future atrophy rates (over the second interval) was explained. In the heterogeneous group, 20.2% of the variance in future atrophy rates could be explained, but slightly less in concurrent atrophy rates (16.2%).
Conclusion
We concluded that variance in brain atrophy rates can partially be explained by clinical and MRI measures of disease. Future atrophy rates in individual MS patients are difficult to predict even when including previous atrophy rates.
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.
•MPH increased attentional and mnemonic performances in the SHR.•MPH decreased impulsive behavior of the SHR.•MPH had no effect on hyperactivity.•Our results do not fully support the predictive ...validity of SHR as an ADHD model.
The spontaneously hypertensive rats (SHR) are the most widely used model for ADHD. While face and construct validity are consolidated, questions remain about the predictive validity of the SHR model. We aim at summarizing the evidence for the predictive validity of SHR by evaluating its ability to respond to methylphenidate (MPH), the most well documented treatment for ADHD. A systematic review was carried out to identify studies evaluating MPH effects on SHR behavior. Studies (n=36) were grouped into locomotion, attention, impulsivity or memory, and a meta-analysis was performed. Meta-regression, sensitivity, heterogeneity, and publication bias analyses were also conducted. MPH increased attentional and mnemonic performances in the SHR model and decreased impulsivity in a dose-dependent manner. However, MPH did not reduce hyperactivity in low and medium doses, while increased locomotor activity in high doses. Thus, since the paradoxical effect of stimulant in reducing hyperactivity was not observed in the SHR model, our study does not fully support the predictive validity of SHR, questioning their validity as an animal model for ADHD.
Attention-deficit/hyperactivity disorder (ADHD) is traditionally conceptualized as a neurodevelopmental disorder that continues into adulthood in up to half of diagnosed cases. In light of current ...evidence, factors associated with the course of the disorder remain unknown. We performed a systematic review of the literature searching for risk markers from childhood that predicted the persistence of ADHD into adulthood. We reviewed 26,168 abstracts and selected 72 for full-text review. We identified data from 16 studies, comprising 6 population-based retrospective samples and 10 clinical follow-ups. We performed meta-analyses of factors evaluated by at least three studies. Severity of ADHD (OR 2.33, 95 % CI = 1.6–3.39,
p
< 0.001), treatment for ADHD (OR 2.09, 95 % CI = 1.04–4.18,
p
= 0.037), comorbid conduct disorder (OR 1.85, 95 % CI = 1.06–3.24,
p
= 0.030), and comorbid major depressive disorder (OR 1.8, 95 % CI = 1.1–2.95,
p
= 0.019) emerged as predictors already presented in childhood for ADHD persistence into adulthood. Further, we suggest that cohort studies should be designed to clarify such an important question for research and clinical practice.
Abstract The exposition to traumatic events related to urban violence is epidemic in Brazil, with rate of 80% in the general population, and is becoming a major cause of post-traumatic stress ...disorder (PTSD). The objective of the study was to compare serum levels of pro-inflammatory interleukin-6 (IL-6) and anti-inflammatory interleukin-10 (IL-10) in PTSD and resilient individuals. We hypothesized that resilient individuals present an attenuated pro-inflammatory and enhanced anti-inflammatory state. We conducted a case-control study comparing 30 resilient individuals and 30 PTSD patients exposed to traumatic events related to urban violence. The groups were evaluated using Self-Report Questionnaire (SRQ-20), Mini-International Neuropsychiatric Interview (MINI) and the Davidson Trauma Scale. For all individuals, blood samples were collected to determine IL-6, IL-10 and cortisol serum levels. All samples were frozen at –80 °C until the assay and were analyzed with the same immunoassay kit and in duplicates. The resilient group presented higher IL-10 levels than PTSD patients mean (CI); 1.03 (0.52–2.08) pg/mL vs. 0.29 (0.20–0.43) pg/mL; P = 0.002. There were no differences in terms of IL-6 or cortisol levels. The results provided evidence for increased levels of IL-10 in resilient individuals when compared to PTSD patients, probably conferring them a better anti-inflammatory response after exposition.
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.
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