Barts-MS rose-tinted-odometer: zero-★’s
It became clear to me at least 6 years ago that we need to go beyond NEDA (no evident disease activity) when treating MS and we have to focus on protecting the end-organ, i.e. normalising the brain volume loss that occurs in people with MS (pwMS). To do this you really need to diagnose and treat MS as effectively as possible early on. From a research perspective, this means a focus on smouldering MS and the mechanisms responsible for the smouldering disease or the ‘real MS’.
This study below is another study showing a link between brain atrophy and cognitive impairment and supports the therapeutic strategy above. The criticism that is alway levelled at the flipping-the-pyramid argument is that too many pwMS will end up on high-efficacy DMTs and then what? My response to this is that if the majority of pwMS end-up on high-efficacy DMTs eventually is a testament to fact that the majority of pwMS need high-efficacy DMTs and hence it is best to get them there as soon as possible (#TreatMSASAP).
This #TreatMSASAP principle underpins our #AttackMS trial design of using natalizumab ASAP after presentation and is aping the management of stroke.
Another argument about flipping the pyramid is safety, i.e. we are putting pwMS at risk of severe adverse events. Yes, we are, but we can derisk a lot of the anticipated adverse events, i.e. the known-knowns and the unknown-knowns (anticipated AEs based on the mode-of-action of DMTs). In any event it is not for the neurologist or HCP to make the call on risk; surely it is up to the person with the disease to make the call?
The following is a recording of my presentation from ACTRIMS-ECTRIMS 2020 that discusses these issues. Please note the presentation is targeting HCPs, but most pwMS should understand it.
Golan et al. The association between MRI brain volumes and computerized cognitive scores of people with multiple sclerosis. Brain Cogn 2020 Sep 11;145:105614. doi: 10.1016/j.bandc.2020.105614. Online ahead of print.
Background: Computerized cognitive assessment facilitates the incorporation of multi-domain cognitive monitoring into routine clinical care. The predictive validity of computerized cognitive assessment among people with multiple sclerosis (PwMS) has scarcely been investigated.
Objective: To explore the associations between brain volumes and cognitive scores from a computerized cognitive assessment battery (CAB, NeuroTrax) among PwMS.
Methods: PwMS were evaluated with the CAB and underwent brain MRI within 40 days. Cognitive assessment yielded age- and education-adjusted scores in 9 cognitive domains: memory, executive function, attention, information processing speed, visual-spatial, verbal function, motor skills, problem solving, and working memory. The global cognitive score (GCS) is the average of all domain scores. MRI brain and lesion volumes were assessed with icobrain ms, a fully automated tissue and lesion segmentation and quantification software.
Results: 91 PwMS were included [Age: 52.1 ± 11.7 years, 64 (70%) female, EDSS: 3.4 ± 2.0, 79 (87%) with a relapsing-remitting course]. Significant correlations were found between the GCS and whole brain, white matter, grey matter, thalamic, lateral ventricles, hippocampal and lesion volumes (Correlation coefficients: 0.46, 0.40, 0.25, 0.42, -0.36, 0.21, -0.3, respectively). Regression analysis revealed that lateral ventricles and thalamic volumes were the most consistent predictors of all cognitive domain scores.
Conclusion: Computerized cognitive scores were significantly associated with quantified MRI. These findings support the predictive validity of multi-domain computerized cognitive assessment for people with multiple sclerosis.