Predictors of long–term clinical response to interferon beta therapy in relapsing multiple sclerosis

Objectives The aim of this study was to identify clinical, magnetic resonance imaging (MRI) and biological markers predictive of long–term clinical response to interferon beta (IFN beta) therapy in patients with relapsing–remitting multiple sclerosis (RRMS). Methods Sixty–eight patients treated with IFN beta were followed over a 6–year period. Relapse rate and disability progression were evaluated throughout the study. We considered suboptimal clinical response to be either the presence of sustained disability progression, or more than two relapses. Baseline and 12–month demographic, clinical and MRI findings, as well as the development of neutralizing antibodies (NAbs) against IFN beta during the first year of therapy were analyzed as predictors of long–term clinical outcome. Results "Black holes" on MRI were the best baseline predictor of disability progression (odds ratio [OR] 6.8; p < 0.001).At 1 year, both male gender (OR 4.9; p = 0.009) and NAbs (OR 7.3; p = 0.003) were independently associated with a high risk of developing subsequent disability. The presence of gadolinium enhancement, both at baseline (OR 4.7; p = 0.005) and on the 1–year MRI scan (OR 7.9; p = 0.002), was the unique variable associated with the number of relapses over the study period. Conclusions Variables assessable within the first year of treatment significantly influence relapse rate and disability progression in patients with RRMS treated with IFN beta. These findings may help clinicians to make decisions regarding therapy regimen over time, and highlight the need for a prognostic algorithm. The study was supported by Industria Farmaceutica Serono Italy.     

The cognitive bias task (CBT) in healthy controls: a replication study

Contextual processing is the selection and bringing "on-line" of internal representations of a task that can be used in planning and mediating goal-appropriate behavioral responses and is a relevant issue that probably is involved in many neurological and psychiatric conditions. The Cognitive Bias Task is a measure of context-dependent responding, is sensitive to quadrant-lesion effects, and interacts with gender. The goal of this study was to replicate and detail more completely the method of context-dependent processing for healthy control patients on the Cognitive Bias Task. The results show the presence of three different cognitive patterns that could biases the response of control patients: context-independent, context-dependent, and mixed. Gender, but not handedness, significantly influences contextual processing, with more females than males producing a context-independent pattern of responding. Test results and the relation of contextual processing in psychiatric disorders were discussed.     

Awareness of illness and outcome in schizophrenia

The purpose of the present study was to investigate whether awareness of illness affects specific measures of outcome in schizophrenia. Patient awareness was evaluated using a shortened version of the Scale to Assess Unawareness of Mental Disorder (SUMD). Patient outcome was assessed by means of the Strauss-Carpenter scale. Our findings indicate that lack of awareness of “negative symptoms” has a considerable impact on outcome: in fact “Social Contacts” highly correlated with Blunt Affect, Anhedonia and Asociality items on the SUMD. Lack of awareness seems then to be a powerful predictor of poor outcome. Received: 11 August 1999 / Accepted: 9 December 1999     

Educational level and age influence spatial working memory and Wisconsin Card Sorting Test performance differently: a controlled study in schizophrenic patients

The influence of educational level and age on executive function, as evaluated by the Wisconsin Card Sorting Test (WCST), and 'working memory,' as evaluated by means of a visual-manual delayed-response task, has been investigated in 25 schizophrenic patients and 35 healthy controls matched for age. Different patterns of correlations between educational level, age and cognitive variables were seen for the 'working memory' task but not for the WCST. No significant correlations between the WCST and the 'working memory' task indexes have been observed. Based on multivariate analyses, poor performance of schizophrenic patients on working memory and executive function tasks was observed; after covarying for the educational level, group differences were no longer significant for executive functions, but the difference in 'working memory' performance persisted. The implications of sociodemographic variables as well as the role of statistical manipulation are evaluated and their differential impact on 'working memory' and executive functions is proposed in further support of these neurocognitive constructs that may be dissociable.     

Correction to: Treatment response scoring systems to assess long-term prognosis in self-injectable DMTs relapsing–remitting multiple sclerosis patients

Journal of Neurology -     

Antioxidant vitamins reduce oxidative stress and ventricular remodeling in patients with acute myocardial infarction

We analyzed soluble vascular adhesion molecules (sVCAM-1), reactive oxygen metabolites (ROMs) level, total antioxidant status (TAS) and telediastolic left ventricular volume (TLVV) in patients with myocardial infarction undergoing reperfusion therapy and treated with antioxidant vitamins (AT) or placebo (P) before and for 1 month after reperfusion. After reperfusion, sVCAM-1 serum concentration, reactive oxygen metabolites level, and TLVV were significantly higher in patients treated with placebo than in those treated with antioxidant vitamins, while TAS was significantly higher in patients treated with antioxidant supplementation. We observed that 48 hours after reperfusion sVCAM-1 (P) vs sVCAM-1 (AT) was 2.03+/-0.5 vs 1.63+/-0.7 microg/ml with p < 0.01; ROMs (P) vs ROMs (AT) were 335.60+/-35.80 vs 307.50+/-47.10 U.CARR with p < 0.05; TAS (P) vs TAS (AT) was 526.47+/-44.24 vs 737.65+/-51.15 micromol/l with p < 0.01; 1 week after reperfusion TLVV (P) vs TLVV (AT) was 125.12+/-29.80 vs 119.40+/-29.40 ml with p < 0.05; 1 month after reperfusion TLVV (P) vs TLVV (AV) was 132.00+/-33.50 vs 123.40+/-21.60 ml with p < 0.05. In the first period after infarction, vitamin treatment improves the antioxidant system and reduces oxidative stress, inflammatory process and left ventricular remodeling.     

Heparin attenuates symptoms and mast cell degranulation induced by AMP nasal provocation

BACKGROUND: Previous studies have shown that inhaled heparin attenuated the airway responses to allergen, exercise, and AMP bronchial provocation, possibly through an inhibition of mast cell activation. OBJECTIVE: The aim of this study was to provide the evidence of in vivo inhibition of human mast cell activation by heparin in a noninvasive model. METHODS: Nine atopic and 6 nonatopic subjects received placebo and unfractionated heparin sodium (5000 IU/mL) 15 minutes before an AMP nasal provocation in a double-blind crossover study design. The nasal lavage was collected from these subjects before or 3, 5, 15, or 30 minutes after the AMP nasal challenge, and concentrations of histamine and tryptase in the nasal lavage were measured. RESULTS: AMP nasal provocation produced considerable sneezing and induced a transient increase in histamine and tryptase release, with peak values achieved at 3 to 5 minutes after the challenge in all atopic subjects. Compared with placebo, inhaled heparin significantly attenuated the release of histamine and tryptase induced by AMP challenge (P=.012 and.004, respectively). Moreover, the AMP-induced sneezing was also inhibited by pretreatment with heparin (P=.016). In nonatopic subjects, AMP did not induce a significant increase in histamine and tryptase release on placebo-treated or heparin-treated days. CONCLUSION: These data suggest that AMP nasal provocation and AMP bronchial provocation cause mast cell mediator release in a similar fashion. In addition, the data support the hypothesis that inhaled heparin plays a protective role against AMP provocation by inhibition of mast cell activation.     

Inhaled lysine acetylsalicylate (L-ASA) attenuates histamine-induced bronchoconstriction in asthma

When administered by inhalation, histamine provokes dose-related bronchoconstriction in asthmatic subjects mainly by a direct activation of histamine H1-receptors on airway smooth muscle. However, little is known of the change in airway responsiveness to histamine after cyclooxygenase blockade. The aim of the study was to investigate the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation on histamine-induced bronchoconstriction in a group of 16 asthmatic subjects. The subjects studied attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg/ml) or matched placebo (glycine solution of 30 mg/ml) 15 min before bronchoprovocation tests with histamine and methacholine in a randomized, double-blind order. Changes in airway caliber were followed as forced expiratory volume in 1 s (FEV₁), and agonist responsiveness was expressed as the provocative concentration causing a 20% fall in FEV₁ from baseline (PC₂₀). Administration of both L-ASA and glycine solution caused a small but significant acute fall in FEV₁ from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to histamine in 13 of the 16 subjects studied, the geometric mean (range) values for PC₂₀ histamine increasing significantly ( P < 0.001) from 1.72 (0.13–5.49) mg/ml to 3.31 (0.36–12.00) mg/ml after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. Acute administration of L-ASA by inhalation protects the asthmatic airways against histamine-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the airways response to histamine in human asthma.     

Tower of Hanoi and WCST performance in schizophrenia: problem-solving capacity and clinical correlates.

We administered a computerized version of WCST, a well established test, sensitive to executive function deficits in schizophrenia that involves many features of cognitive processing, and of Tower of Hanoi, a test that may offer cognitive challenges more specifically related to planning and sequencing, to 28 schizophrenic patients and 28 matched controls to examine a worthwhile question regarding the relative ability of these two tasks to differentiate schizophrenia and normal groups as well as exploring the relationship of these two instruments to clinical variables. The schizophrenic patients performed significantly worse than normal subjects both on Tower of Hanoi test and on WCST. The discriminant analysis identified in a multivariate way a pattern of indexes that differentiate the two groups. This pattern, characterized by specific indexes of WCST and TOH, could suggest the existence of a common underlying factor that determines the cognitive impairment in problem-solving of schizophrenics. These findings and the relationship with positive and negative symptoms have been discussed in the light of the model of the impairment in the internal representation of context information.     

Increased risk of death from COVID-19 in multiple sclerosis: a pooled analysis of observational studies

Journal of Neurology - To estimate whether the risk of death from COVID-19 in patients with multiple sclerosis (MS) exceeds that of the general population. We conducted a pooled analysis of cohort...