Best Neuroprotection is to stop inflammation from occurring.


We hear about the “real MS” as so terms as if it is un-treatable….but if we want to stop nerve damage, we have to deal with the inflammarory reaction as quickly and as effectively as possible.

Retinal and brain damage during multiple sclerosis course: inflammatory activity is a key factor in the first 5 years.Pulido-Valdeolivas I, Andorrà M, Gómez-Andrés D, Nakamura K, Alba-Arbalat S, Lampert EJ, Zubizarreta I, Llufriu S, Martinez-Heras E, Solana E, Sola-Valls N, Sepulveda M, Tercero-Uribe A, Blanco Y, Camos-Carreras A, Sanchez-Dalmau B, Villoslada P, Saiz A, Martinez-Lapiscina EH.Sci Rep. 2020 Aug 7;10(1):13333. doi: 10.1038/s41598-020-70255-z.

Understanding of the role of focal inflammation, a treatable feature, on neuro-axonal injury, is paramount to optimize neuroprotective strategy in MS. To quantify the impact of focal inflammatory activity on the rate of neuro-axonal injury over the MS course. We quantified the annualized rates of change in peripapillary retinal nerve fiber layer, ganglion cell plus inner plexiform layer (GCIPL), whole-brain, gray matter and thalamic volumes in patients with and without focal inflammatory activity in 161 patients followed over 5 years….The increased rate of neuro-axonal injury during the first five years after onset was more prominent among active patients, as reflected by the changes in GCIPL thickness (p = 0.02), whole brain (p = 0.002) and thalamic volumes (p < 0.001). Thereafter, rates of retinal and brain changes stabilized and were similar in active and stable patients. Focal inflammatory activity is associated with neurodegeneration early in MS which reinforces the use of an early intensive anti-inflammatory therapy to prevent neurodegeneration in MS.

More evidence

First-ever treatment in multiple sclerosis.Pantazou V, Pot C, Du Pasquier R, Le Goff G, Théaudin M.Rev Neurol (Paris). 2020 Aug 5:S0035-3787(20)30626-3. doi: 10.1016/j.neurol.2020.05.014. Online ahead of print.

Background: The current treated MS population is very different from that of patients in randomized clinical trials.

Objectives: To study the long-term efficacy and tolerance of fingolimod (FTY) and dimethyl fumarate (DMF), both available as first-line treatment in early-treated treatment-naïve MS patients.

Methods: Retrospective analysis of 75 patients from our prospective MS registry fulfilling the inclusion criteria: FTY or DMF as first-line treatment, treatment initiation within 36months of disease onset and treatment duration>12months.

Results: Demographics and MRI characteristics at baseline were similar in both groups (FTY 55 patients, DMF 20), but patients on FTY had higher pretreatment clinical activity (P=0.008). Twenty-two percent of patients in the FTY group and 15% in the DMF group had highly active disease. At last follow-up (mean: 44.2, SD: 17.3months), the majority of the patients were still on treatment while 54.5% of FTY and 65% of DMF patients reached NEDA 3 status (P=0.444). Both treatments significantly decreased relapses and occurrence of new T1 Gd-enhancing lesions (P<0.001). The main reason for discontinuation was disease activity without severe side effects on either treatment.

Conclusions: Our findings support efficacy and tolerance of both drugs in early-treated treatment-naive MS patients, arguing in favour of efficient early immunomodulation in MS patients. Both drugs significantly reduced the incidence of new relapses and Gd-enhancing lesions on treatment with FTY being more frequently prescribed than DMF, especially in patients with evidence of higher clinical disease activity.

COI. Multiple none considered relevent

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  • MD,

    The “real MS” / “smouldering MS” are terms which Prof G has been using in presentations for quite a while. I was quite happy knowing that I had two courses of an anti-inflammation (focal inflammation) anti-relapse therapy which shut down all relapses and resulted in no visible activity on my annual MRI.

    Prof G has given me sleepless nights by proposing that focal inflammation and relapses are not MS – just a response to the real MS / smouldering MS which goes on unabated. His argument is quite convincing ie even those on effective DMTs still accumulate disability.

    We seem to be at another MS chicken and egg conundrum. What comes first – smouldering MS which results in focal inflammation / relapses or focal inflammation which then leave smouldering MS? Another unanswered MS question as with T v B cells, inside / out or outside / in disease, maybe a virus, maybe autoimmune, inflammatory or neurodegenerative ie which comes first… Too many unanswered questions for anyone to badge themselves as an MS expert!

    If the two mouse doctors, Prof G, Prog K and NDG sat in a room together for half a day, how much agreement would there be as to what MS is, how it starts, how it progresses, how to stop it? This blog is very informative for patients but has also exposed to me how little is really known about the disease.

    • Which come first….Birth 🙂

      In the animals, it is clear what comes first.

      Perhaps to address your question there are people where relapses have been shut down…and unfortunate accidents have occurred….the pathologists should have the answer…but we have seen time and time again that they can’t agree, indeed there are question marks about whether the case which set this debate (oligodendrocyte damage with few inflammatory cells) in motion was actually MS….If radioisolated syndrome/prodrome is the norm, the real MS would have been occuring years before the Prineus case died…..they would have had oligoclonal bands meaning the immune system was established in the CNS, even if it could be see in a few tissue sections. If you look at a hit and run the car is nowehere to be seen.

      Put us in the same room for half a day…. I wish best we will get is a virtual room

    • The key to the Chicken and egg conundrum was provided by Charles Darwin; the egg came first but it was not laid by a chicken – it was laid by a chicken ancestor. This ancestor that was probably almost, but not quite, a chicken and one more bit of evolution in its offsping and there’s your chicken. Unless it was hybridization event, in which case less chicken-like ancestors could be possible. Bet they tasted of dinosaurs.

  • Nothing new, and nothing hopeful for someone like me with slow PPMS, whose treatable damage (with current DMTs) most likely mainly occurred long before clinically apparent symptoms emerged.

    • It depends on the finances of the charities. They are more or.less.ready to go it.covid 19 may have.set.them.back months or years

  • Forgive my very naive question, but if “Focal inflammatory activity is associated with neurodegeneration early in MS”, I’m not clear why it’s not, as general neurological wisdom finds, in the slow burn of axonal damage later on.

    Should we take it that early inflammation sets off some variety of relatively autonomous smouldering that carries on eating away at myelin long after the prerequisite inflammation has left its mark? If science allowed, is it likely that all “secondary” nerve damage would be traceable to inflmamation? Or is there a second pathology at work – with the kind of complex comorbid action that you folks can understand and I can’t – aacting in tandem with the MRI-legible events that respond to anti-inflammatories?

    And crudely, does this tell us anything about the way decisions to halt DMTs should be made?

    Thanks for reading.

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