Normalized visibility ratings observed in the control experiment as a function of SOA for four subjects.

<p>The control experiment featured only dichoptic conditions, in which targets and masks were presented to different eyes. The two subjects depicted in the left half of the figure, the left eye received blurred stimuli to mimic loss of visual acuity. The two subjects depicted on the right, the right eye received blurred stimuli. The bar charts show the temporal position of the individual minima (SOAmax).</p

Stimuli used in the control experiment.

<p>Stimuli depicted in a) and b) are identical to the stimuli used in the main experiment. Stimuli depicted in c) and d) were created by blurring the contours with a Gaussian kernel while keeping overall stimulus energy (i.e. the average brightness of the display) constant.</p

Individual Fit results–Main Experiment.

<p>Individual Fit results–Main Experiment.</p

Illustration of stimulus setup and procedure.

<p>(a) The display was viewed through a mirror stereoscope. The gray squares were constantly presented to ensure binocular fusion. (b) Example of a trial sequence, here with a target presented to the right eye, and a mask to the left eye, both above the fixation point. Negative SOAs refer to trials where the mask preceded the target. (c) Illustration of the assignment of keys to perceived target contrast. The same figure (with German labels) was part of the on-screen instruction.</p

Average SOA_max (ms) for the control group (N = 8) and the patients (N = 6), depending on the eye to which the target was presented.

<p>The mask was always presented to the opposite eye. Error bars depict the 95% confidence interval of the mean. Each connected pair of circles represents SOA_max-values from a single subject / patient.</p

Significant relationship between physicians’ last statement on continuation or discontinuation of natalizumab and the proportion of patients continuing or stopping therapy.

<p>Physicians’ last judgment on continuation of therapy on a visual analog scale from 0 to 25 points (1 = ‘rather continue natalizumab’, 25 = ‘rather discontinue natalizumab’) had an influence on the proportion of patients continuing/discontinuing natalizumab.</p

The control subjects' and the patient's mean FA values of different ROIs as calculated from DTI. Significance levels (* p<0.05, ** p<0.001, *** p<0.0001).

<p>The control subjects' and the patient's mean FA values of different ROIs as calculated from DTI. Significance levels (* p<0.05, ** p<0.001, *** p<0.0001).</p

Is the risk of progressive multifocal leukoencephalopathy the real reason for natalizumab discontinuation in patients with multiple sclerosis?

<div><p>Background</p><p>Progressive multifocal leukoencephalopathy (PML) is one of the major risks of natalizumab therapy. Despite introduction of the currently employed PML risk stratification algorithm, the incidence of natalizumab-associated PML cases is not decreasing.</p><p>Objectives</p><p>We addressed the following questions: How do natalizumab-treated multiple sclerosis patients and their treating physicians assess and deal with PML risk? Is PML risk the real reason for natalizumab discontinuation?</p><p>Methods</p><p>699 natalizumab-treated multiple sclerosis patients and 99 physicians were included in this prospective observational study. Questionnaires were completed at 5 different time points. Patients were stratified into 5 subgroups according to the presence of PML risk factors (prior immunosuppression, anti-JCV antibody status, treatment duration). Patients with prior immunosuppression (n = 30, treated by n = 7 physicians) were excluded from analyses, because patient numbers were too small. Patients’ anti-JCV antibody index was not considered because data recruitment ended in 2014. Using Bayesian network and regression analysis, we examined the relationship between different patient- and physician-related factors and patients’ discontinuation of natalizumab.</p><p>Results</p><p>Patients of all subgroups and physicians assessed the PML risk as low. Overall patient adherence to natalizumab was high (87%). Only 13% of patients discontinued therapy. Natalizumab treatment cessation was associated with different patient- and physician-related factors (physicians’ assessment of general PML risk, number of treated patients per year, natalizumab treatment duration, relapses during the course of study) upon which only physicians’ judgment on treatment continuation, patients’ perception of personal PML risk, and JCV seroconversion showed significant relationships.</p><p>C<i>onclusion</i></p><p>According to the currently employed risk stratification algorithm, the <i>objective</i> PML risk probably doesn’t play a dominant role in a patients’ decision to continue or stop natalizumab treatment. The decision-making process is rather guided by <i>subjective</i> views and experiences of patients and treating neurologists. Treating physicians should consider this discrepancy in their advice to improve the risk-benefit-ratio for the individual patient.</p></div

Examples of histopathologic findings.

<p>A: Pannecrosis, parietal lobe. HE stain. B: Neuronal necrosis (arrow), frontal lobe. HE stain. C: glial scarring of the white matter. GFAP stain. D: Inflammation of the white matter (black arrows: macrophages, black arrow head: microglia). CD68 stain. E: Patchy loss of myelin structure in the occipital lobe. Klüver-Barrera stain. F: Astrogliosis of the putamen (white arrow heads: astrozytes). GFAP stain.</p

Assessment of personal PML risk at visit 1 to 5 for patients continuing and discontinuing natalizumab (NTZ).

<p>Patients discontinuing NTZ (green) assessed the personal PML risk higher on a visual analog scale from 0 to 25 points (0 = ‘low’, 25 = ‘high’) in all visits than patients continuing NTZ (blue) (*p < 0.01; **p < 0.0002; ns = not significant).</p