Review: Differential Cognitive Impairment for Diverse Forms of Multiple Sclerosis

The article reviewed here is an open-access article ‘Differential Cognitive Impairment for Diverse Forms of Multiple Sclerosis’ by Gonzalez-Rosa et al and freely available here.  In the abstract, the authors write that

‘The present results suggest a cognitive impairment in the information processing in all of these patients…..This suggests a silent deterioration of cognitive skills for the BMS [Benign Multiple Sclerosis] that is not usually treated with pharmacological or neuropsychological therapy‘

The main question that can be asked here is how do the results, analysis and discussion in the article fit with the above conclusions?

Firstly the researchers have recruited two groups of Multiple Sclerosis subjects. One group has the relapsing-remitting form of Multiple Sclerosis characterised by periods of deterioration and then improvement while the other have received a diagnosis of ‘Benign Multiple Sclerosis (BMS)’ (see Appendix for link to another study on Benign Multiple Sclerosis). I wasn’t clear on how the diagnosis of Benign Multiple Sclerosis had been arrived at. I could not find an explicit reference to the sampling method for the three subject groups and I note that the sample sizes are relatively small with 45 subjects included in the study.

The Posner paradigm was used. This involves a visual display which shows an arrow. A target appears on the screen at the location of either the valid position (indicated by an arrow on the screen) or the invalid position and the subject has to respond by pressing the appropriate button. Both the accuracy and speed of responses are measured and both right and left hands are used which I assume is to avoid any bias from handedness. The underlying assumptions for this paradigm are that it taps into attentional mechanisms – disengagement from gaze target, movement to new target and engagement with new target. They also presented the subjects with standard stimuli and measured the evoked potentials in 4 leads.

Figure 1 shows a comparison of the measures for the invalid and valid trials. The confidence intervals for all of the pairings appear to overlap suggesting that amongst the many possibilities there could be no significant difference between the means. In other words the distinction between valid and invalid trials wasn’t particularly interesting.  Figure 2 shows the Evoked Response Potentials in the four leads in the different groups and the authors note the lack of a certain response – the N1 response in both MS groups. Figure 3 shows a 3d scatterplot of the three subject groups on axes denoting amplitude of frontal N1, response time and latency P300. The three groups are separated into clusters and although I found it difficult to judge the locations of the clusters from the diagram, it appears that the benign MS groups values lie further from the control group than the relapsing-remitting group. This apparent relationship from the visual inspection of the scatterplot also appears to hold for both % of correct responses with the RRMS and controls appearing closer to each other than the BMS group to either. The same holds for the reaction times and this suggests the importance of understanding the methodology of the selection of subjects for the study.

Nevertheless when the researchers performed an ANOVA on the comparisons they found that the control group responded significantly faster than either the RRMS or BS groups. They also found that the valid reaction times were significantly faster than the invalid reaction times using this analysis. Although there were interesting findings in terms of the evoked potentials, the authors draw conclusions about the cognition. In terms of the conclusions given in the abstract it can be stipulated that they researchers have demonstrated a significantly worse performance on a very specific task which involves focusing on a simple visual cue and responding to a visual target that appears on the screen. The magnitude of the increase in reaction times for the BMS group is somewhere in the region of an extra 50ms and so in this study at least it can be argued to be of significance. It would be interesting to see a larger replication study with use of additional psychometric tests.

Appendix

Article on Benign Multiple Sclerosis by Hawkins and McDonnell, 1999.

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