Tuesday, 11 August 2015

Cleansing the waters - is there a role for plasma exchange in MS?

Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients.
Ehler J, Koball S, Sauer M, Mitzner S, Hickstein H, Benecke R, Zettl UK. PLoS One. 2015 Aug 5;10(8):e0134583. doi: 10.1371/journal.pone.0134583. eCollection 2015.


Objectives :Experience with therapeutic plasma exchange (TPE) for acute relapses in clinically isolated syndrome (CIS) or multiple sclerosis (MS) patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.
Participants: Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18–69 years).
Outcome Measures Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS) scoring.
Results A clinical response to TPE was observed in 65 out of 90 patients (72.2%), with marked improvement in 18 (20.0%) and moderate improvement in 47 out of 90 patients (52.2%). The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001). Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001), no disease modifying drugs (p = 0.017), gadolinium-positive (Gd+) MRI lesions (p = 0.001) and EDSS ≤ 5.0 before TPE (p = 0.014). In the multiple logistic regression analysis only the detection of Gd+ MRI lesions was significantly altered (p = 0.004).
Conclusion Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd+ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.



Plasma exchange

As a clinician this paper challenges our current thinking of managing MS, at least in the early stages. It's a retrospective study, but without a doubt plasma exchange appears to be superior to steroids as a treatment option (see figure below). The Gd+ suggests that maybe this would be an option in patients with relapses.

So what would be the proof of concept for plasma exchange? If you believe that MS has miasma/scourge of nasties floating around in your blood, then cleansing the body of this makes sense. This would include things like myelin targeting antibodies, cytokines, heat shock proteins, complement etc.

Logistically, it would be a nightmare to set up. Steroids trump this by being relatively safe (aside from avascular necrosis of the hip), having an oral option and the IV version which can be given by district nurses at home if required. Conversely, plasma exchange is unlicensed, expensive and can kill you (secondary to line infection and sepsis, too much fluid being removed, drop in clotting factors, STD's etc.).

Nonetheless, I would consider it an option in tumefactive MS where the presentation is ghastly, with reduced conscious level, seizures, aphasia (inability to talk) etc. As our experience/success rates improve - diversifying into CIS and RRMS (for relapses) should be on the cards.


Glucocorticosteroid treatment and therapeutic plasma exchange in clinically isolated syndrome and multiple sclerosis patients. A) Response to glucocorticosteroid treatment in CIS and MS patients. B) Response to therapeutic plasma exchange in CIS and MS patients. C) Different responses to therapeutic plasma exchange in CIS and MS patients. D) Development of medianEDSS values during therapeutic plasma exchange. * p = 0.01 (CIS versus SP-MS), ** p = 0.002 (RR-MS versus SP-MS), *** p = 0.001 (EDSS before versus after TPE).

10 comments:

  1. This should be broadly disseminated. I am one of the victims of the current worldview that steroids is the best treatment for relapses - repeated to me multiple times in the hospital during an acute relapse which led to a quick diagnosis - but also continuing deterioration on steroids (I ended up wheelchair bound for a month - and I was functioning normally several days prior to this relapse). In the end, I did recover most of the lost function - but it took many weeks of a rehub, outpatient PT, and continuing exercising over the years. Preventing at least some of this damage would go a long way.
    I also think that plasma exchange in acute relapses can be combined with immunosuppresants - you remove the nasty stuff first, but then stop its rapid regeneration in the body.

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  2. I know two people who have plasma exchange as a treatment of a strong outbreak ... But it has to be done using immunosuppressive together?

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    1. The effects of plasma exchange are not long-lasting and therefore will need to be combined with an immunosuppressant.

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    2. When I read this publication on plasma exchange I ask me if the problem of MS resides in immune cells properly or somewhere in the brain, well hidden ... Who find out for sure exactly deserve the Nobel Prize ...

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  3. The more and more I read about MS, the more and more I wonder why it is not a managed through a multi disciplinary approach. My partner with MS has received a lot of help and information from a hematologist, in addition to the advice and help she receives from neurologists. Sometimes my partner's neurologists cross the line and give advice on areas outside their expertise (such as cancer risks for a patient with prior cancer history). It's a wild wild west out there.

    Bojana

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    1. My neurologist looks after more than my central nervous system. He diagnosed illnesses the specialists in their fields didn't.

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  4. "Too many cooks spoil the broth", be advised that too much advice is counterintuitive and that applies for MDT decisions...

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    1. If he didn't, I wouldn't be here now. That also applies to MDT decisions. I'm lucky to have doctors that treat me as a person, not a scientific experiment.

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    2. Anon, maybe I should explain myself more clearly. These are pitfalls that clinicians realise quickly in their practice. I'm not saying that a neurologist cannot diagnose other conditions. We attend conferences and training sessions to be able to do this very thing at the best of our abilities. But my personal views are (and this is an opinion) that the success of an MDT team is dependent on how well they can work together (and it goes without saying that I only realised this after working with a very good team)...

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    3. We need MDT staff that are willing to question and challenge other members. If not, the process would be redundant.

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