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.

One patient's story

This month I was privileged to hear from Keith whose wife Lisa has recently been diagnosed with CLIPPERS. She has had a tough time as she had a much more acute onset of symptoms than I did and suffered several relapses before the CLIPPERS diagnosis enabled her to receive the right treatment regime. Keith has been keeping an on-line journal about his experience which is updated pretty much in real time. You can read their story here (note that the entries are most-recent first). Keith is also keen to find out as much as possible about how best to support a recovering CLIPPERS patient through treatment.

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 Brazillian CLIPPERS case

The Peak District in September

To date, the majority of reported CLIPPERS cases have been from the United States, Europe and Australia. As awareness of the condition spreads, cases are being reported from other parts of the world. Recently the first Brazillian case report has been published where a 49 year-old first presented with CLIPPERS-like symptoms in 2001; of course CLIPPERS wasn't first published in a scientific journal until 2010. 

Interestingly, straight away this patient received pulse-steroid treatment which is now fairly standard when CLIPPERS is suspected; his symptoms improved. Unfortunately, Multiple Sclerosis was suspected and so other drug treatments which were not effective were subsequently used. In 2014, after significant deterioration, treatment for CLIPPERS was begun (Prednisolone and Azathioprine). There was then marked improvement of the lesion appearance in MRI but much less clinical (i.e. patient) improvement.

Although this is only a single case, it adds to the evidence that early diagnosis and treatment is important in CLIPPERS, as there may be progressive damage over time which cannot be completely reversed if treatment is delayed. I began steroid  treatment 3 months after I had my first symptoms which I think was quite fast. In my case my first symptom was diplopia and I was lucky to be spotted by someone in an eye clinic (once I'd been back a couple of times) who was worried about my worsening symptoms and referred me quickly to a neuro-opthalmology clinic. From there, I was lucky to be seen by a neurologist who was also sufficiently worried - especially when I failed all the balance tests - to get me admitted quickly to a neurology ward for in-patient investigation. It still took a month in hospital (in 2011) before they realised CLIPPERS was the likely culprit and began treatment. I think given that CLIPPERS was not widely recognised in 2011, this was still very fast and I am profoundly grateful to the people who pushed me rapidly through the healthcare system.

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.

Another cautionary tale

Chewing the cud, or at least the hay, in Kent.

A recent article reminded me about the dangers of classing myself simply as "someone with CLIPPERS". Probabilities are funny things; when considering someone who is otherwise well, the lifetime chance of them getting diagnosed with CLIPPERS is very small indeed. The lifetime chance of them getting diagnosed with CLIPPERS AND some other condition is even smaller. However, for someone who already has a diagnosis of CLIPPERS, their chance of getting some other condition is just the same as anyone else (unless CLIPPERS has some mysterious protective effect which seems unlikely).

In their article "Stroke mimicking relapse in a patient with CLIPPERS syndrome" (unfortunately, not freely available), Dr Lefaucher and colleagues from Rouen describe exactly this latter set of circumstances.  A 52-year old man who had been diagnosed with CLIPPERS four years previously presented with double vision and ataxia, both common symptoms of CLIPPERS. After running some tests, a particular kind of stroke affecting a similar region of the brain as CLIPPERS was diagnosed and the patient was treated accordingly. In the paper, the authors briefly discuss whether disease processes associated with CLIPPERS could have made this kind of stroke more likely in this patient. They suggest that damage to small vessels after inflammatory disease (i.e. like CLIPPERS) could be a risk factor for subsequent stroke. However they also say, with a slightly odd choice of words, that the association between CLIPPERS and stroke in this case is simply "fortuitous" - I think I prefer the term "coincidental" but I'm pleased they concede that it could be just "one of those things" (my phrasing).

As someone in reasonable health, apart from CLIPPERS, and approaching middle-age this article reminded me that just because I drew the short straw in terms of rare cerebellar disease, doesn't mean that I am immune from any of the more common conditions that can appear as we age. So it's definitely worth doing the usual things to stay healthy to avoid as far as possible any other surprises.

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.

Still in remission from cerebellar disease ...

... is the official word from my neurologist who I saw in his clinic in London last week. I did a few familiar tests such as walking "heel-to-toe"; he remembered that I had previously said I practiced this one at home to check if I had symptoms so he also wanted to make sure I couldn't still do it simply because I had been practicing so often! The other two tests were to do with eye coordination. One involved moving my finger from my nose to  his finger (and back again) while he waved his finger around in front of me. The other involved holding my head still and tracking his finger movement (left-right-up-down and then swiftly left-to-right) by only moving my eyes.

A medical student was present who helped with some of these tests and said I had nystagmus. I was surprised as I knew I had a lingering very mild nystagmus for a while, but I thought that had resolved and hoped it wasn't a sign of recurring CLIPPERS symptoms. Fortunately, it turned out that the student had been moving his finger too far/fast beyond the extremes of my left/right vision; everyone gets nystagmus if you try and track at these extremes.

We had a short discussion about continuing treatment. Regular and long-term readers of this blog will know that I have been maintained on Azathioprine alone (100mg twice a day) for three years now. We agreed that because of the uncertainty surrounding the disease, the possible catastrophic consequences of a relapse and my good tolerance so far of this drug, that this treatment should continue.

Interestingly, I recently came across a letter (unfortunately not freely available to read) about long-term CLIPPERS management which mentioned one or two cases of patients on various drug combinations staying well, or at least staying stable, for several years. Long term management is bound to become more of an issue in the future but it is not at all clear whether there is a single optimal treatment strategy or whether different treatments should be tailored for different patients. It may be as much luck as anything else that I have benefited from Azathioprine so far.

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 in the news

The Detroit News (not a publication I was previously familiar with) has recently run an article about CLIPPERS based on the experience of Roger, a military veteran in Michigan. You can read the article here:

http://www.detroitnews.com/story/life/wellness/2015/05/25/worlds-st-case-disorder-michigan/27944751/

(I can't guarantee this link will stay working forever as it is on an external site).

It's an interesting story and reminded me of my own experience when after several weeks of uncertainty one of my doctors produced this article about this "thing called CLIPPERS" which seemed to describe quite accurately what I had. I did wonder about the title: "World's 51st case of disorder is in Michigan". I haven't counted lately, but I suspect the number of published cases may be around (or probably exceed) 51 as they say in the article, but I also suspect the number of diagnosed cases worldwide runs into the hundreds. Whatever, it is still a very rare condition and stories like this which help raise the profile can only be a good thing. I hope Roger continues with his recovery from CLIPPERS.

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.

More blood.

Filled tubes, 9 of them.

So, following on from last time, I finally managed to get my blood sample collected for the Mayo CLIPPERS study. In fact, I had no problem filling all 9 tubes - I have good veins apparently. Hopefully it survived the trip over the Atlantic with FedEx and will contribute in some small way to helping understand more about CLIPPERS. 

Two warts merged into one.

As of the beginning of June, I am over four years since first symptoms and still taking Azathioprine with few side-effects. Apart from occasional blips in liver scores, I have a few warts (7ish) which is apparently quite common on Azathioprine. They are confined to fingers with a few periungual ones for good luck. Not very pleasant, but could be worse - I had them blasted with cryotherapy recently which will hopefully help. That's enough about warts.

Finally, I'm not sure how long this has been live, but CLIPPERS now has a short entry on Radiopaedia (think of Wikipedia, but for doctors)

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.

Blood

A box of stuff.

A bag of tubes.

I realise there's been a bit of a gap between posts recently - sorry about that.  In the interim I received the kit from the Mayo Clinic to allow my blood to be transported half-way round the world within a day or so of being drawn; I never imagined one day my blood would be flying to America. When it arrived, the box was big, very big. However I soon discovered that most of the volume was taken up by the polystyrene container which will hopefully ensure everything arrives intact. There is a little bit of paperwork, but most of it has been filled out already and fortunately, as a non-US citizen, I don't need to fill out the tax declaration. 

As someone who is nearing 4 years since first CLIPPERS symptoms, and has had over 3 years of normal life on Azathioprine, it would be nice to think there was something interesting in my blood. I suspect though, that the key will be to get sufficient patients enrolled that some subtleties start to emerge from the CLIPPERS population as a whole.

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.

Glimpses of CLIPPERS Neuropathology

Seeing blobs on contrast-enhanced MRI and not being able to tie my shoe-laces up is one thing, but figuring out the root cause(s) and mechanism(s) of CLIPPERS is complicated. In fact it is probably far more complicated than I imagine, and I already think it is complicated. One of the most valuable resources for scientists investigating CLIPPERS is access to brain-tissue for direct investigation. Until some suitable animal model displaying CLIPPERS-like features is found, we have to rely on sporadic and sometimes opportunistic access to brain-tissue samples from patients. 

I have a couple of reports from such studies in my CLIPPERS folder. These are hard for me, as a layman (and someone who left biology behind a long time ago) to discuss as I am aware of my lack of understanding and cautious about passing it on. Anyway, here goes ....

The first report is from a conference last year (The International Congress of Neuroimmunology). The title nicely summarises the study:  "Neuropathological evaluation of four Danish cases of CLIPPERS: Evidence of generalized neuroinflammation but no pre-lymphoma". (Unfortunately the full text does not seem to be publically available, however as a conference paper it was less than half a page of text anyway - a bit mean of the publisher though.) One of the four cases had been autopsied so presumably the whole brain was available for analysis. Perhaps the most interesting finding was that some broader evidence of inflammation was found in brain tissue - "A similar, but less prominent, T-cell infiltration was found in the normal appearing cerebral cortex" - which would not light up in contrast-enhanced MRI i.e. not in visible lesions. Perhaps the most reassuring finding was that "Our study does not suggest that CLIPPERS is a pre-lymphoma condition".

The second report was of a single, quite severe case, of CLIPPERS in an elderly woman who subsequently died of other causes. In their paper "Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): postmortem findings", the authors found less extensive inflammation - "The dura, cortical gray and white matter, ..., were unremarkable." They also remarked that "... our case does show that evolution to lymphoma, even after several years, is not inevitable in CLIPPERS."

So, in these small studies, there are already some interesting agreements and disagreements. It is possible the the variation in CLIPPERS presentation and patients may explain things, or differences in the experimental methods which I have not picked up on. Small steps.

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.

Mayo CLIPPERS Study Update

It must be Spring.

A very quick update/reminder about the CLIPPERS study at the Mayo Clinic. I had a very brief email conversation with Dr Tobin about the study recently. He confirmed that they are still actively recruiting and keen to collect data on as many patients as possible. In particular they are committed to tracking recruits at intervals in the future to gather information about outcomes. Treatment effectiveness, susceptibility to relapse and long-term effects of CLIPPERS are some of the big issues they want to study. They are also actively analysing the preliminary volunteer data they have already and will update us about this in due course. So if anyone is interested in finding out more about this study please look on the CLIPPERS repository page for more details.

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.

Rare Disease Day

I was reminded that today is Rare Disease Day 2015. So I will simply post the message from Rare Disease UK and suggest that everyone reading this blog takes some small feeling of recognition in being part of a much larger collection of affected people world-wide.

It's Rare Disease Day today! Today we are paying tribute to the millions and millions of parents, siblings, grandparents, spouses, aunts, uncles, cousins, and friends whose daily lives are impacted and who are living day-by-day, hand-in-hand with rare disease patients.
We know that many of you have a rare condition or care for someone who does. Yet you have helped RDUK to ensure that policy makers, public authorities, researchers, and health professionals understand that rare diseases are a public health priority. So would like to thank you - our dedicated members - for a all the hard work you and support you have shown. We couldn't have done it without you!

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.