Prof G has the MS community go it wrong?
In this week’s NEJM there is an insightful perspective by Louise Aronson on ageing and driving.
Aronson. Don’t Ruin My Life — Aging and Driving in the 21st Century. N Engl J Med 2019; 380:705-707.
Louise quotes the American poet Donald Hall, who explains in Essays After Eighty how life is irrevocably and excruciatingly changed when a person must let go of their car: “For years I drove slowly and cautiously, but when I was eighty I had two accidents. I stopped driving before I killed somebody, and now when I shop or see a doctor, someone has to drive me. …Old age is a ceremony of losses.”
Although this refers to old age the same can be said for someone with MS. MS is a sequence of losses. Does it have to be this like this? I hope not, but to get to this position we need to go beyond NEDA.
I am running one of our Barts-MS teaching programmes this week in which a case was presented by one of the delegates. The lady, who is in her early thirties, has a diagnosis of relapsing MS and is NEDA, off therapy for 5 years, i.e. no relapses and no new T2 lesions. However, when you look at her sequential MRIs next to each other it is clear that she has progressive brain volume loss. She has NEDA-3, but clearly, something else is happening to her brain. I suggested to the neurologist looking after this patient to interrogate her in detail, i.e. to measure her brain volume, send her for cognitive testing, arrange for a more objective interrogation of her neurological functioning and to do a lumbar puncture to assess if she has inflammation and ongoing damage as measured by CSF neurofilament levels. In other words, don’t rely on what we have now to assess her MS disease activity.
The problem we have is that we have created a beast called NEDA and the wider MS community now think evident disease activity or EDA (relapses and focal MRI activity) is MS. EDA is obviously not MS. It is clear that EDA in untreated patients is a very poor predictor of outcome. IF EDA was MS it would predict outcome regardless of being treated or not. In other words, EDA fails one of Prentice’s criteria for being a surrogate marker of MS.
Despite writing frequently on the topic that MS is not due to relapses and/or focal MRI activity the dogma seems to stick. I have arguably helped create NEDA as a treatment target and have been responsible for some of its stickiness as a treatment target. Can I admit I am wrong? NEDA is a useful construct, but it is now becoming a barrier to treating MS properly.
If I was a behavioural psychologist I would be referring to NEDA as the new cognitive bias. We need to shift our worldview of MS away from an MRI worldview. What we should be doing is creating a biological worldview of MS and asking what is happening in the ‘field‘ or the brains of people with MS. We have to explain why end-organ damage is ongoing despite switching