The idea factory: how big a problem is smouldering MS? Are we fooling ourselves? #IdeaFactory #MSBlog #MSResearch
"I did a follow-up MS clinic yesterday and had a few MSers who returned for decisions after having had annual monitoring MRI scans. Three of them had breakthrough disease on MRI, i.e. new or enhancing lesions, when the current scan was compared to the one from a year ago. All of these MSers thought they were relapse free and stable. How could this be? When I probed them with questions all three of them had had intermittent symptoms that were clearly minor relapses. One had sensory symptoms affecting a leg, another was had an episode of being more unsteady and noticing a deterioration in their walking distance and another had tripped and fell and noticed some transient weakness in their foot. My first insight is that we are simply not capturing all relapses with our current definition. We need a better way of monitoring this clinical activity without being too intrusive on MSers lives; several MSers are not comfortable with a daily diary as it takes too much time and reminds them every day of their MS. Any suggestions?"
"Another insight is that most MSers with subclinical relapses (MRI activity) do not feel right; adjectives used are 'very tired', 'exhausted', 'fatigued', 'out of sorts', 'I could sleep all day', 'my brain fog is back' and 'I just don't feel well'. I am sure these symptoms are compatible with MS-related sickness behaviour. Sickness behaviour is triggered by inflammation; the inflammatory mediators, or messengers, signal to the brain to slow down and sleep. From an evolutionary perspective this behaviour is triggered in sick animals to conserve energy to allow the body to recover. Anyone who has had influenzae will know what sickness behaviour feels like. May be we need a way of measuring this sickness behaviour between annual MRI scans? Any thoughts?"
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The MS Iceberg |
"Another insight is that all these MSers were on injectable 1st-line therapies. These therapies were probably taking the edge off the relapses, i.e. making them less frequent and clearly less severe. The downside of this is that none of these MSers would be classified as having highly-active or rapidly evolving MS and therefore would not be eligible for the most effective therapies we have to treat MS. They would have to go through intermediate efficacy DMTs. In other words the less effective drugs are creating a large number of MSers with smouldering MS, that is partially under control, but not under control enough when applying the zero-tolerance litmus test. In other words these DMTs do not stop the shredder, they only slow it down. This is why we really need to get biomarkers into clinical practice that measure the hidden disease activity so that we can target the bottom of the MS iceberg and stop the slow burn that results in end-organ damage. At the end of the day our treatment target must be to prevent disability, not to simply slow the rate of its accumulation down. Zero tolerance has to be the goal. Do you agree? Or do you disagree?"
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"I am seriously considering cutting down on clinical practice; I simply don't have enough hours in my day. However, seeing MSers, and managing MS in real life, stimulates thinking and generates ideas. In short, clinical practice is an Idea Factory."
CoI: multiple
Labels: end-organ damage, Ideas Factory, NEDA