Monday, 3 November 2014

Steps in the right direction ... hopefully

Rainy London
To counteract the grey skies, shortening days and dipping temperatures in the UK, there has been a hint of progress in our understanding of CLIPPERS. In their paper Effective antituberculous therapy in a patient with CLIPPERS: New insights into CLIPPERS pathogenesis, Dr Mele and colleagues describe a CLIPPERS case which was initially diagnosed and treated as suffering from CNS tuberculosis. After 18 months of treatment the patient no longer had significant symptoms and only slight MRI abnormalities. 

The interesting thing is that 6 months after tuberculosis treatment was stopped, the patient relapsed and then improved again when tuberculosis treatment was restarted. My reading of the paper is that the first treatment round should have guaranteed that no tuberculosis was present yet they still improved when treated for it again. At this point the patient was re-appraised and treated for CLIPPERS with Prednisolone at which point more marked improvement was seen.

So the interesting result is that improvement in a CLIPPERS patient was seen whilst being treated with drugs not usually used for CLIPPERS. The authors note that one of these drugs (rifampicin) is anti-inflammatory and is also thought to be helpful for rheumatoid arthritis. They speculate in some detail about the possible mechanisms by which this drug may operate.

This is a very interesting article and I don't pretend to understand the detail. As I am not a doctor, there may be short-comings that I don't appreciate (not least the usual problems of diagnosis) so some caution is required. However, the authors should be applauded for not claiming too much. They report a single interesting case and discuss possible consequences including the potential use of response to rifampicin in diagnosis, but do not go over the top. In my opinion, this work is perhaps more valuable for providing possible clues and new directions for research rather than suggesting alternative CLIPPERS treatments. It is also the sort of paper that may well attract some interesting letters from other academics in the next few months. I will keep watch.

Read other articles in this series at Living With CLIPPERS.

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Wednesday, 8 October 2014

Extending CLIPPERS (again)?

As time goes on, there seem to be more case studies which veer away from the characteristics of the original cohort described by Dr Pittock. In this recent report "An extended chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids phenotype", Dr Lane and colleagues describe an interesting new case with some unusual features. (Unfortunately full text for this article is not available on-line, but those interested could try emailing the senior author Dr Robin Howard and asking for a pre-print.)

The earliest symptoms of the woman in this case study were initially right-sided facial weakness with abnormal cold sensations on her left leg. It was over a year before scans revealed CLIPPERS-type brain lesions. However in this case there were more wide-spread lesions ("cortical involvement") than in some other reported cases and she suffered seizures. The CLIPPERS symptoms improved immensely after 5 days of high-dose steroids (although at 500mg/day rather than the 1000mg/day I received). Of interest to me  is that this patient was then moved onto a tapered dose of Prednisolone starting at 60mg/day (like me) and subsequently onto Azathioprine (like me, but dosage not reported). She has apparently remained well 6 months on. 

My experience is not directly comparable to this patient as my symptoms were much more in the "classic" vein (i.e. limited to double-vision, balance, speech, symmetric facial and limb numbness). However interesting to see the use of Azathioprine when it seems more common to prescribe Methotrexate or Cell Cept. I'm not convinced Azathioprine is a magic bullet but suspect that different people react to the disease and the treatment in different ways; but I am not a doctor.

Interestingly, my doctor said recently he still has no idea why some people seem to relapse on these "steroid-sparing" agents but remain well on steroids, as both treatments should have essentially the same action.

In other news I finally got round to sending my consent forms back the Mayo for their study.

Read other articles in this series at Living With CLIPPERS.

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Tuesday, 16 September 2014

Historical CLIPPERS cases

Holiday snap from Southern Italy
I recently read an interesting short communication entitled "CLIPPERS among patients diagnosed with non-specific CNS neuroinflammatory diseases" by Dr Kerrn-Jespersen and colleagues from hospitals in Denmark. As regular readers of this blog will know, the term "CLIPPERS" was first used in 2010 in the now well-known paper by Dr Pittock and colleagues. They observed a consistent pattern of symptoms and treatment responses in a group of patients over several years which led them to the conclusion that a single previously unreported condition was responsible. 

CLIPPERS is very rare, which is presumably why it was not identified earlier. However, it is reasonable to suspect that there were other cases out there "in the wild" before 2010; these cases were presumably either diagnosed as something else or diagnosed as some generic inflammatory condition. In the Danish paper, the authors searched their hospital records between 1999 and 2013 for cases with descriptions reminiscent of CLIPPERS. After some investigation they found 3 patients (= 12.5% of their initial list of suspects) who justified being reclassified with a CLIPPERS diagnosis. This number may seem small, but it is from a limited number of European centres over a limited time-period and suggests there could be significant further cases out there.
Perhaps the most important practical outcome of the study for us patients is that the follow-up of their 3 cases confirmed that early and sustained treatment was important to minimise longer-term problems.

Read other articles in this series at Living With CLIPPERS.

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Wednesday, 20 August 2014

Brief Repository Update

Colin the Caiman
I received an email from Dr Tobin at the Mayo Clinic recently to update me on their CLIPPERS Respository project. This is a systematic approach to CLIPPERS research which involves gathering as much information about patients as possible in one place to enable detailed research. If you have a diagnosis of CLIPPERS and want to take part, you can read more on the CLIPPERS Repository page.

Anyway, they are currently focussing on patients who had tissue samples available and they have 12 enrolled to date which they are very pleased with. This data is enabling them to take a more comprehensive look at the common features of the condition across different people with less doubt about the possibilities of other diseases being present. There should be some more news about this in the near future.

They are also still very much interested in recruiting people with a CLIPPERS diagnosis but who didn't have tissue samples taken. These people (like me) are still a valuable resource and will form a larger cohort which can be used in the next phase of the research. I have signed up and will update you about the process when I get my enrolment kit.

Apparently, some other laboratories are talking to the Mayo about the possibility of performing different analyses on some of the samples. I think this is particularly exciting as it means there may be a competitive element which will help drive the research. I am hopeful that with this kind of approach some progress can be made in finding out more about what CLIPPERS really is, and how to best treat it.

Read other articles in this series at Living With CLIPPERS.

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