CPPERS, PPERS, LIPPERS or CLIPPERS?

There's a storm coming ...

A very interesting paper has recently appeared by Dr Taieb and colleagues about treatment strategies in CLIPPERS. I will return to this theme in a subsequent post but wanted to focus on something more basic, namely whether CLIPPERS is a single condition. In this recent works which reviews the majority of previously published cases, Dr Taieb proposes some division of CLIPPERS into sub-types. My reading of this is that it is a sub-division of convenience based on symptoms, investigations and response to treatment rather than any new insight into underlying biology. Nevertheless, it has been apparent for some time that there is immense variability under the CLIPPERS "umbrella".

Dr Taieb lists 5 key features of CLIPPERS which I paraphrase more simply here: (i) characteristic signs and symptoms, (ii) characteristic pattern of lesions seen in MRI, (iii) prompt response to steroid treatment, (iv) no competing diagnosis, (v) characteristic appearance of brain biopsy. So as a reminder, CLIPPERS stands for "Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids". With this in mind, Dr Taieb suggests that sufferers with a single attack and the first 4 or 5 key features are "PPERS" or "LIPPERS" respectively and sufferers with more than one attack and the first 4 or 5 key features are "CPPERS" or "CLIPPERS" respectively. 

I think the key interpretation of this system is that it is designed to reflect the available evidence about each case and make comparing cases easier. However it is influenced by the range of tests done (i.e. not everyone has brain biopsy) and the success of treatment. For instance, to date I have had a single attack and I declined a brain biopsy so I have the first 4 features and am "PPERS", but this can't distinguish between someone who has successful treatment and someone who simply has a disease that doesn't relapse.

In the diagnosis of Multiple Sclerosis, one of the criteria is that damage must have occurred at two different times - it is an inherently relapsing disease. However, presumably this is only true while effective treatments which could be given after a single episode are not available. I think the same is true of CLIPPERS and that when treatment strategies improve, the role of the "relapse" in diagnosis may dwindle.

(NOT A DOCTOR)

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.

CLIPPERS Cases Update

Trees by Bonfire Light

Dr Tobin and colleagues from the Mayo Clinic in the US and from Ghent in Belgium recently presented a paper at the ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis) conference. The paper is called "Defining a clinical, radiological and pathological signature of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids)" and that it was presented at a meeting primarily associated with Multiple Sclerosis emphasises that these brain disorders shouldn't be considered in isolation.  The work concerns efforts for a better working definition of CLIPPERS to aid with diagnosis and involves finding the key things which CLIPPERS patients have in common. In this still relatively small group of 34 subjects, eleven were excluded because of various findings which conflicted with what is known about CLIPPERS. This shows the difficulties of the whole diagnostic process for CLIPPERS.

One thing I found interesting, is that of the 23 subjects remaining, gait ataxia was the most common symptom (21/23) with diplopia (double vision), although the second most common symptom, lagging behind (13/23). In my case, diplopia was the first symptom with ataxia problems following, first with balance problems and later on with coordination and speech problems.

Another interesting thing is that all 11 patients in the study who stopped steroid treatment suffered symptom recurrence; it is not stated whether these patients were on other immuno-suppressant medication or not. I have managed to stay off steroids while taking Azathioprine but it is not clear whether I am just lucky or whether there is something which distinguishes my disease from others. I should avoid the temptation to read too much into this paper though, as conference presentations are usually early work in very short format which are followed up later by more substantial journal publications. Clearly though, this shows there are on-going collaborative efforts between researchers in the US and in Europe to move towards a better understanding of how CLIPPERS presents in patients.

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.

CLIPPERS Without Steroids?

One key thing that characterises CLIPPERS is that it responds to steroids in the first instance. So characteristic is this that "Responds to Steroids" is the "RS" in CLIPPERS. Everyone who is treated for CLIPPERS, at some point or another, receives steroid treatment, which for many patients means high-doses of intra-venous Prednisolone.

 

A recent case study (but only a single case) hints that other treatment paths may be possible. I must stress that a single case in a condition that is hard to diagnose like CLIPPERS can't be definitive, but this is interesting none-the-less.

 

This patient had diagnoses first of Multiple Sclerosis and subsequently of neurosarcardosis (both conditions that were considered in my case also). Treatment was with hydroxychloroquine which is an anti-inflammatory used in the treatment of neurosarcoidosis. (Interestingly, the FAQ here, suggests that Prednisolone is the drug of choice for neurosarcoidosis, showing once again that there are many overlapping conditions which can be treated somewhat similarly.) The patient had good resolution of symptoms however, after their symptoms, tests and records were re-examined, the diagnosis was changed to CLIPPERS; the patient has remained well on maintenance doses of hydroxychloroquine since. Also interestingly, Dr Pittock at the Mayo Clinic, had previously tried hydroxychloroquine in one CLIPPERS patient but did not have as good results as in this case study.

 

The authors suggest hydroxychloroquine be considered as an alternative treatment for CLIPPERS because it is well-tolerated by patients, although it is not without side-effects. It will be interesting to see if this study affects treatment decisions in any future patients and whether the good results gained here can be reproduced.

 

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.

Aside: You say CLIPPERS ...

... I say CHIPPERS.

I'm sure that, before you found this site, you had to wade through lots of Google links for the Los Angeles Clippers and various pieces of personal grooming equipment. So I wondered if a more distinctive acronym could be squeezed out of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids. Fortunately, there are many web-sites out there to help with forming acronyms. I used Acronym Creator which worked pretty well.

As I used the same words which make up CLIPPERS as input, some of the results are quite contrived, or don't use all of the terms properly. Still, some of the better ones (which I have adapted slightly) were:

CHIPPERS     Chronic lympHocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids

CRIPES       ChRonic lymphocytic Inflammation with Pontine perivascular Enhancement responsive to Steroids 

CaLIPERS     Chronic Lymphocytic Inflammation with Pontine perivascular Enhancement Responsive to Steroids

CHIMERaS     CHronic lymphocytic  InflaMmation with Pontine perivascular Enhancement Responsive to Steroids

fLaPPERS     chronic  Lymphocytic inflammation with Pontine Perivascular Enhancement Responsive to Steroids

CaROLINES     ChROnic Lymphocytic INflammation with pontine perivascular Enhancement responsive to Steroids

CyCLOPS     ChroniC LymphOcytic inflammation with Pontine perivascular enhancement responsiv to Steroids

CavaLIERS     Chronic Lymphocytic Inflammation with pontine perivascular Enhancement Responsive to Steroids

Perhaps inevitably, none of these trip off the tongue quite as well as CLIPPERS. So we are probably stuck with it, at least until someone renames it Pittock-Keegan Syndrome ....

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.

CLIPPERS And Other Nasties

Station Cat - seen on the way to work occasionally

News about CLIPPERS is a bit thin on the ground at the moment. Hopefully, like the retail industry, the journals are saving everything up for the Christmas rush. In the mean-time, I was flicking through a paper called "Autoinflammatory grey matter lesions in humans: cortical encephalitis, clinical disorders, experimental models" (unfortunately not open access but you can read the abstract). Hidden away was a brief mention of CLIPPERS, essentially commenting that it is a new example of a disease which has a " ... unspecific inflammatory reaction which may also affect grey matter". This much we know, but it is interesting that there are now attempts in the literature to compare and contrast CLIPPERS to other diseases - much of this paper was about Multiple Sclerosis which was a candidate diagnosis in my case, at least for a week or so. In fact this paper approached things from a mechanistic rather than a disease perspective - it considered a particular way in which damage to the brain could occur and then discussed the various different disorders which could cause it.

The other thing which I found both interesting and worrying last year, was the sheer number of different things which can afflict us. When I was in hospital the doctors would tell me they were going to test for all sorts of things which I had never even heard of. Mostly I didn't even know whether to worry about the diagnosis if I got one. If I'd known about all these different maladies before I was investigated I'm sure I would have got really stressed out trying to work out which it could be. As it turned out, with CLIPPERS I didn't know whether to worry about the diagnosis and I'm not sure the doctors did either!

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.

A Not So Curious Case of CLIPPERS?

This month another CLIPPERS case study appeared, a report about a 56 year old man who I'll call "Sheldon" for ease of discussion. Although these single subject studies are limited in the sense that small numbers of cases don't allow general conclusions about CLIPPERS to be drawn, they are still of interest given the relatively small number of published reports to date. To me the interest in the recent report from Biotti et al is that this case is unremarkable and seems to fit fairly well with the bulk of the other reports - and with my own experience.

A Curious Case of CLIPPERS?

One of the problems with diagnosing CLIPPERS is that there isn't a definitive test. So a case for CLIPPERS has to be constructed from the available evidence and by excluding other conditions. The definition of CLIPPERS is still somewhat vague with some open questions about whether cases which don't fit the established pattern are CLIPPERS, or some other unrecognised condition, or a combination. A case recently reported as CLIPPERS by Guillaume Taieb and colleagues demonstrates these problems.

Deconstructing C.L.I.P.P.E.R.S.

So what is CLIPPERS anyway? Well the acronym doesn't give much away and expanding it out isn't immediately informative to the non-specialist. So I'll break CLIPPERS down into it's component parts to show how CLIPPERS is really just a description of the syndrome. As usual this is my interpretation of a complex phenomena about which I don't have special knowledge (apart from experiencing it first hand!) so a full explanation will require some more book work. (AKGTQENR3XWH)