Systematic review of CLIPPERS studies

Wind-battered trees on Brean Down

One of the difficulties in studying conditions like CLIPPERS is their rarity meaning that there are comparatively few cases to draw from. CLIPPERS, with it's variability of symptoms and outcomes and difficulties in concrete diagnosis has additional challenges. However, now that there have been over ten years of scientific publications on CLIPPERS there are opportunities to get a better overview by combining together earlier work. Dr Al-Chalabi and colleagues from the University of Toeldo published a paper in 2022  titled "Clinical characteristics, management, and outcomes of CLIPPERS: A comprehensive systematic review of 140 patients from 100 studies" to try and achieve this. A systematic review is where a collection of previous works are combined following a protocol which strives to ensure quality and minimize bias to hopefully come to stronger conclusions than might be possible looking at the individual studies. In the case of this review, the "clinical characteristics, treatment strategies and outcomes" of CLIPPERS were assessed.

My reading of the review is that the authors drew together some common themes from the individual studies but that the amount of variability and uncertainty still hindered their ability to draw firm conclusions, even in over 100 nominal CLIPPERS patients. They found 60% of their cohort were male and the mean age of onset was 46 years (which is very close to the age I first got symptoms). The most common (but not the only) symptoms, in order, were ataxia , diplopia, and dysarthria; my own experience was diplopia first, then quite quickly followed by ataxia, and latterly by some dysarthria just as I began treatment. They also found that around 15% of the patients studies had some form of malignancy which presumably means CLIPPERS wasn't their ultimate diagnosis (but I am not a doctor). In terms of long-term treatment, Azathioprine and Methotrexate, were the most common, but not the only, drugs. 

The authors also report that a shorter time on steroids was associated with an increased risk of CLIPPERS relapse which, to me, is the most interesting of their conclusions, possibly, and very unscientifically and with no evidence, because I have long had a gut feeling that longer steroid tapers might be better. The authors suggest that, going forward, steroid tapers should be very slow, although they don't state what "slow" means - presumably months?

These studies are important and as well as making the most of previous studies can hopefully direct future research.

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Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

2016

The Round Table (allegedly) in Winchester

Just a quick note to wish everyone who follows this site - or even just visits occasionally - a happy and prosperous 2016. I will endeavour to keep you all updated with any news about CLIPPERS I hear about. As always, if anyone has anything they want to share then please get in touch. Please note that I am changing my preferred email address for the blog to wrcrum@hotmail.com but entries to the old one should still get through.

Read other articles in this series at Living With CLIPPERS.


Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

I'll Have Mayo With That ...

... Light Mayo Obviously

I came across an interesting article on the website of the Mayo Clinic recently. Doctors from the Mayo were the first to characterise CLIPPERS and of course define the CLIPPERS acronym. The article - Multiple Sclerosis Mimickers - discusses conditions that can be mistakenly diagnosed as Multiple Sclerosis in the clinic. CLIPPERS is number two on the list, after Neuromyelitis Optica and before lymphoma. I'm sure I'm not the only one with first-hand experience of the diagnostic challenge that CLIPPERS presents. Really, the article is about recognising the contribution that Mayo researchers have made to our understanding of these diseases and conditions. Particularly interesting is how cases of what is now thought to be CLIPPERS were investigated by Dr Keegan very early in his career and then later in conjunction with Dr Pittock.

If anyone reading has picked up any interesting CLIPPERS-related snippets from the Mayo let me know and I'll post them here.

Read other articles in this series at Living With CLIPPERS.

Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

News Flash

The most important CLIPPERS paper of the year so far has just appeared. It's called "Long-Term Outcomes of CLIPPERS in a Consecutive Series of 12 Patients" by Dr Taieb and colleagues. I haven't had time to digest this paper properly as it is quite involved (and I'm not a doctor) but some very brief points from a first reading.

Back In Black

CLIPPERS Long-Term
(As usual, please note I'm not a doctor so don't take this as gospel.)

The paper focuses on the pattern of relapses in 12 people diagnosed with CLIPPERS, treated with cortico-steroids and followed over months or years. Dr Taieb says that "Secondary progression was not observed" - in Multiple Sclerosis secondary progression means "sustained build up of disability, independent of any relapses". So this study suggests that there isn't an underlying disease process continuing to cause damage after symptoms have been treated with cortico-steroids. This is good news.

Relapses
Patients who remained on steroid doses at 20mg/day or higher tended not to get relapses but patients who did get relapses continued to respond to repeated high doses of steroids. Dr Taieb found that early treatment of relapses was important to prevent worsening of symptoms during the relapse or continuing problems. So I guess it's good news that CLIPPERS remains treatable but not so good news that it can return after the first episode. We have to remember though that this is still only 12 patients so this paper represents an important step along the way rather than a definitive study.

Still Missing
One important missing piece of the puzzle is the effectiveness of alternative immunosuppressant therapy. Three of the patients described by Dr Taieb were moved on to Cyclophosphamide and one on to anti-CD20 (Rituximab) treatment with one subsequently relapsing. Of particular interest from my point of view is that there is no data on the long-term effectiveness of Azathioprine although there is some existing evidence (from other smaller studies) that Methotrexate can be effective.

I Am An Experiment

I have been on < 20mg Prednisolone / day since November 2011 and since June 2012 I have been taking only Azathioprine and am still well. So I guess we'll see what happens ....

Read other articles in this series at Living With CLIPPERS.

Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

About Living With CLIPPERS

This blog is about a recently characterised brain disorder called CLIPPERS which produces a characteristic pattern of lesions (spots) in the brain. These lesions interfere with normal functioning in many tasks related to coordination, balance and (double) vision amongst others. I am a 44 year-old unremarkably healthy male who was diagnosed with CLIPPERS in September 2011. CLIPPERS is controversial because it's diagnosis is circumstantial at the moment and so there isn't any straight-forward test which identifies it. This also means that a diagnosis of CLIPPERS can be changed if the observations no-longer fit the pattern. It it is quite possible that in a few years it will be considered a special case of another disorder or there will be turn out to be several different kinds of CLIPPERS with their own patterns of progression or response to treatment.