Intrathecal steroid treatment for progressive MS

I
Are you willing to have 5 lumbar punctures to improve your progressive MS? #MSBlog #MSResearch

“If you have progressive MS you may find this study compelling. The administration of a long-acting steroid into the spinal fluid, alternate days, for 10 days results in a significant improvement in function and a reduction in markers associated with inflammatory damage. Wow!”


“When you read the paper, however, you will realise that this is a small study involving 21 MSers and it was open-labelled. In other words all subjects received the therapy so that both MSers and investigators knew what the study subjects were getting. Therefore the treatment response could have been due to a bias; i.e. MSers wanting to get better and the assessors wanted to find a positive result. This is why we have to do randomized double-blind placebo-controlled trials to try and minimize any bias in the results.”



“This study, however, provides pilot data and hopefully it will be taken forward into the next phase as a randomized double-blind placebo-controlled study to see if these results can be reproduced in a blinded way. I like this study because it investigates spinal fluid and study subjects were prepared to have 5 lumbar punctures. The latter indicates to me, in combination with our surveys, that if you have progressive MS most progressive MSers are willing to have multiple lumbar punctures to assess new treatments for progressive MS.”

“I would like to congratulate these investigators on a difficult study and I would encourage them to take it forward with a further study. They owe it to the field and to the MSers who volunteered for this study to do another study. If not we should debate the ethics of studies like this. Is it right to consent MSers to participate in a study that involves an invasive procedure and exposes them to risks, if a positive result doesn’t trigger a more definitive clinical study?”




Müller et al. Reduction in the free radical status and clinical benefit of repeated intrathecal triamcinolone acetonide application in patients with progressive multiple sclerosis. Clin Neuropharmacol. 2014;37(1):22-5


BACKGROUND: Previous open trials performed repeated intrathecal application of the sustained release steroid triamcinolone acetonide every third day in MSers with progressive multiple sclerosis and described enhanced walking abilities.



OBJECTIVES: The objectives of this study were to demonstrate the efficacy of 5 triamcinolone administrations every other day and to describe their effects on the amount of inducible free radicals in cerebrospinal fluid.


SUBJECTS/METHODS: Clinical ratings, determinations of maximum walking distance, and execution of an instrumental peg insertion test were performed at baseline and on each day after a triamcinolone injection in 21 MSers with progressive multiple sclerosis. Induction of free radicals was assessed in cerebrospinal fluid before each triamcinolone application by electron spin resonance spectroscopy.


RESULTS: Scores for multiple sclerosis improved, walking distance increased, and necessary intervals for the peg insertion procedure were shortened. The amount of inducible free radicals decreased.


CONCLUSIONS: Repeat triamcinolone application improves dysfunction of upper and lower extremities even when administered 5 times only and in series every other day. The declined potential for free radical synthesis may be caused by the anti-inflammatory effect of triamcinolone. It may contribute to suppress the smoldering, chronic inflammation, particularly in spinal lesions of patients with progressive multiple sclerosis. The enhanced arm function hypothetically reflects the effect on cervical and brain lesions due to the hypobaric features of triamcinolone.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

21 comments

  • Looks interesting, could you explain a little more of the mechanism of action ? (In layman's terms)

    Regards as always

    • Sorry Mouse, but what do you mean by this?
      My apologies if it wasn't taken from this site, but I know of some to believe that PPMS is the result of inflammatory processes trapped behind the BBB, do you believe this to be the case?
      Why is it that there haven't been too many trials conducted via intrathecal administrative routes?
      As a young (24) newly diagnosed PPMS'er I am desperate to try anything regardless of the lumbar punctures involved.

    • I think you've been on the wacky backy Prof Mouse. Can't make any sense of your posts today. When you've reentered the land of the living, i'd be grateful for your thoughts.

    • Sorry it was a phone post.

      If it works in progressive MS via intrathecal route it supports the case of an immune response/or virally infected B cells behind the blood brain as the problem…This type of treatment failed in non relapsing progressive MS so either the relapsing element allowed the antibody to enter the brain to work or that relapsing disease is responsive to peripheral (i.e in the blood) control. However if it does not work it addes further weight that progressive MS is not a problem of T and B cells.In this case some people will need to re think their position.

      There is inflammation and then there is inflammation some may think T and B cell inflammation but there is gial response this is also inflammation, I suspect that it is the latter element that is partuiculalrly importnat

    • Mouse, you mentioned above that this type of treatment failed in non-relapsing progressive MS. Has that been the case in specific B cell depleting monoclonal antibodies?
      I know in PPMS intrathecal methotrexate has been tried off label and has apparently had some success, does this type of treatment affect B cell numbers though?

      http://clinicaltrials.gov/show/NCT01719159 – this trial is looking at Intrathecal Rituximab in PPMS. Has this been tried intrathecally before?

    • Sorry Mouse, I know you so many other new posts have popped up since this one. But have their been any studies where intrathecal monoclonal antibodies (specifically ritixumab) have failed in PPMS, I have been unable to find any. Other than the intrathecal methotrexate results published by Dr Saddique, as far as I am aware though methotrexate does not impact B cell numbers though?
      Or am I incorrect?

    • The trial of intrathecal in ritixumab in SPMS is ongoing due to report in 2016.
      Double Blind Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients With Low-Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe)

      However clinical trials .gov says it is still recruiting which would mean a 2017

      I am not aware of studies using intrathecal antibodies in MS

      Here is the intravenous delivery results in PPMS
      http://onlinelibrary.wiley.com/doi/10.1002/ana.21867/full

    • Looks promising, but I doubt there will be trials due to the generic status of Methetrexate. If I was a progressive I might try this.

  • The participants willingly consented, the risks were known, there was reason to believe the procedure could help their MS, and in fact, whether it was due to the placebo or the procedure, their MS did improve as a result. Ethics seem fine. Follow-up research would be good. Getting these results into the literature might spark some other group altogether to do further research, so that is a possible good outcome also.

    • The point being made is if you do not have plans to see the project through you should not start as it is false ope

    • Sorry I can't give advice, that's ProfGs and the other Neurs department, except to say discuss this with your neuro, It is an experimental approach without proven benefit and the people doing the study need to do the next studies t demonstrates it woks and it is safe

  • Can you interview one of the researchers of this study?
    It is a bit of hope in a disease where not much hope exists.
    I would like to know why they won't do a bigger follow on study,and I want to know how the patients are doing. Do they have to have this treatment for the rest of their life?

    • They are a German group maybe ProfG knows them.

      A bigger study….if they don't then either they belive it is not worth it or surely they have t

      Will it be a cure…..not sure it would be

  • If it helps with walking that is huge.
    If possible,please ask the team behind it for an interview. It is always worth listening to their point of view.
    The researchers say they don't feel its ethical to do double blind studies,probably because it's an invasive procedure.
    I find it hard to believe that people can experience better walking as a result of placebo.

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