Friday, 5 December 2014

Nothing to see here (probably)

A birthday card I saw
  recently - seriously!
It's all been a bit quiet on the CLIPPERS front lately, so apologies for the slightly sporadic updates at the moment. Another one of these complicated single-case studies has appeared though, so I'll give you a quick run-down. The essential feature of this 62-year old woman's story is that she was diagnosed with CLIPPERS after an episode of shingles which was concentrated on her left ear, eye and face. There is quite a lot of detail about different treatments and symptoms but essentially, when CLIPPERS symptoms first appeared, a left-sided brain lesion was seen on MRI which later developed into a more classical CLIPPERS pattern of lesions towards the back of the brain. This is an interesting case, but as is quit common at the moment, one that is so unusual it is hard to draw too many firm conclusions. I picked up on a couple of things in the paper though.

Firstly the authors speculate that (my paraphrasing) shingles and CLIPPERS in this case are related due to the "time-course" and "laterality". So the time-course means that one follows the other; but just because  the bus arrives after I stand at the bus-stop doesn't mean that I caused the bus to arrive by standing there - correlation versus causation. Secondly, "laterality" means "same-side"; so here, the shingles manifested on the same side as the subsequent brain-lesions. However, for the sake of argument consider that the shingles were completely unrelated to CLIPPERS and were a random occurence (the so-called "null-hypothesis"). Then there is a 50% chance they would manifest on the same side as the initial CLIPPERS lesion even if they had nothing to do with CLIPPERS. Of course, if we see more cases like this then the arguments for time-course and laterality strengthen.

To be fair the authors do go on to say that they "do not believe that the CLIPPERS syndrome is directly caused by the ... viral infection" and flag well the parts of their discussion which are speculation. I hope these cases keep being reported as my impression is that the diversity of CLIPPERS cases appearing over the last couple of years suggests that it could be part of a much larger puzzle concerning a variety of more common brain conditions.

It will be interesting to see if any more cases involving shingles appear. I had facial shingles in 2014 (also on the left-side) after developing CLIPPERS in 2011. In my case, shingles was almost certainly a consequence of immune-suppression from CLIPPERS treatment and being generally run-down. I am pleased to report, that in my case at least, shingles has not caused any resurgence in CLIPPERS symptoms.

Read other articles in this series at Living With CLIPPERS.

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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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