2019 Update

I'm acutely aware that the interval between posts on this blog is steadily lengthening. The reason for this is simple - CLIPPERS simply isn't affecting my day-to-day life much. My current schedule is: take medication twice a day, renew prescription every two months, get blood test every 3 months, see consultant every 12 months ... and that's about it. In other regards I live normally apart from being a bit careful going down stairs. Of course it may not always be like this. I may eventually have some malign consequence of being on these drugs for so long. This could in itself be serious or force me to switch medication. I could have some unrelated health problem which has the same effect. And then, all bets are off.

In parallel, as far as I can tell, researchers are still working on CLIPPERS, presenting new exotic case-studies and gradually gaining some more understanding of what it does. One recent letter succinctly sums up the current state of affairs for diagnosis of new patients and things haven't changed much: "its lack of specific lab findings, poorly understood pathogenesis, and variable symptoms, making it a clinical and radiological diagnosis of exclusion." If you are diagnosed with CLIPPERS you have probably had the following conditions excluded first "neurosarcoidosis, central nervous system Behçet's disease, vasculitis, central nervous system lymphoma, lymphomatoid granulomatosis, Bickerstaff brainstem encephalitis, chronic perivascular infectious process, glioma, central nervous system demyelinating disease, and Langerhans cell histiocytosis"

On the other hand, CLIPPERS is now sufficiently recognised that a recent paper examined the diagnostic costs involved for two patients who had differing numbers of tests but the same outcome in terms of treatment. The cost was approximately $176,000 versus $12,000. Given the diagnostic problems discussed above this seems to me quite a dangerous publication. The authors do comment on reducing invasive testing being good for patients - I agree - and following criterion reccommended by Dr Tobin, but the emphasis is on cost comparison even in the title. Skimping on diagnostic work-up when the consequences of mis-diagnosis are so huge and there is no definitive test for CLIPPERS  is foolhardy and I hope cost doesn't become an issue for proper diagnosis.

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.

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.

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.

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

Yet Another Curious Case of CLIPPERS

 A very interesting variant on CLIPPERS which may offer more research clues has recently appeared. In the paper, "Neurotropic T-cell lymphocytosis : a cutaneous expression of CLIPPERS",  a patient is described who satisfies the current diagnostic criteria for CLIPPERS. However, in addition this person also suffered from sub-cutaneous ("beneath skin")  lesions for some years before, and after, their CLIPPERS diagnosis. The authors points out the similarities in the composition of the skin lesions compared with what is observed in CLIPPERS brain lesions. They make the point that sampling  tissue outside the brain to test for CLIPPERS would be very helpful for diagnosis. However, in this case a brain biopsy for direct comparison was not available so at least one key part of the puzzle is currently missing. 

This is certainly the only case like this that I have read about; the observations are intriguing. I think that time will tell whether this turns out to be a key insight or an interesting aside.

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 linked with MS again.

Another case study has appeared, this time originating  from Japan. This concerns a single subject (33 year old male) who displays enough symptoms to be considered a CLIPPERS sufferer. I'm sure I'm not the only one who reads these things and mentally ticks off the list of symptoms we have in common. This is one of those cases which I don't relate to particularly as I had a different set of symptoms (e.g. I didn't have scanning speech and retained my ability to walk - with difficulty). However CLIPPERS is hard to ring-fence because of the diffuse nature of the disease and I know the symptoms can vary quite a lot both in their type and their intensity. The pattern of lesions in this patient also looks more extensive than I had - compare my scan here with the patient brain in figure 1a - which may explain some of the differences.

The authors are reporting this case for the record without speculating too much. They suggest that CLIPPERS could be a syndrome rather than a disease - this is regularly discussed in the various papers. They also suggest in passing, that the similarities with Multiple Sclerosis mean that CLIPPERS could have something fundamentally in common with it. Here, "could" is the key word, as lots of things "could" be possible but there doesn't seem to be enough evidence (disclaimer: I am not a doctor) to suggest a firm linkage yet.

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.

The Eyes Have It ...

I went to the optician today for a regular (if infrequent) eye check-up. Inevitably when I was asked "Have you had any trouble with your eyes?" a conversation started about diplopia and how, in my case, it turned out to be of neurological origin (i.e. CLIPPERS) rather than because of any defect with my eyes.

One thing that was interesting (although hopefully not in the Chinese sense) is that I apparently still have a very slight nystagmus (involuntary eye movement) which is only visible when looked for down a microscope. This had been noted before, when I still had other CLIPPERS symptoms, but I had assumed it had cleared up along with everything else. Maybe there is some residual damage somewhere - at one point my consultant warned me I might have double vision for good too. Anyway as I can't detect it and it doesn't affect my vision at all I'm not going to lose too much sleep over it. I'll  make a mental note though, because if it gets worse over time it might indicate some renewed CLIPPERS activity.

 

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.

Cutting-Edge Questions and Tedious Jobs

Tedious Jobs

So now all the excitement is over for now it's back to CLIPPERS. Twelve months ago  I was being admitted for investigation at the NHNN with diplopia, ataxia and numb feelings in my hands, arms and feet. Today I spent four hours cleaning the conservatory roof balancing precariously on a step-ladder. This time last year minus a week or so I remember walking up to the local bank and finding it hard to stay on the pavement (it wasn't a narrow pavement). Cleaning the conservatory roof up a ladder definitely wasn't an option then but not being able to see or walk properly now seems a long-time ago. However, I remain vigilant as there's always the chance the symptoms might come back and if they do I want to catch them early. 

    For now though still not much to report. I'm still doing fine on Azathioprine and not expecting the regime to be changed (unless my blood test next week shows anything dubious). 

Cutting Edge Questions

In research-land Drs Keegan and Pittock recently had a short editorial published entitled "Cutting-edge Questions About CLIPPERS". As many of you probably know, Keegan and Pittock were involved in the first scientific papers to recognise and name CLIPPERS as a distinct syndrome. In this short article they advise caution in diagnosing CLIPPERS as the newly reported cases seem to be diverging in their appearance compared with some of the early cases. They also note that even brain biopsy does not give a definitive diagnosis but just excludes other conditions. They urge further work to provide firm diagnostic criteria and monitoring of existing patients so that recurrence can be rapidly treated. All sounds very sensible. I suspect we'll know a lot more in a year or two especially if the rate of diagnosis continues to rise.

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.

Once More Unto the Breach, Dear Friends

Six months ago I first got symptoms of what I now know is probably CLIPPERS. This week it's time for two days of reassessment, fortunately as an out-patient this time. This also coincides with the last few days of my reducing steroid course which so far has done it's job and kept CLIPPERS at bay.  So with the benefit of hindsight, time for a brief recap of the last few months.

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.

Why I've Got CLIPPERS ...

... as suggested by a variety of people.

When something unexpected happens it's a natural reaction to think about the cause. For medical conditions establishing cause is often part of the diagnostic process. However there are many illnesses for which there is no obvious cause. Put another way it's hard to find a common link between people which might either explain the cause or at least predict who is more likely to be affected. So far with CLIPPERS there hasn't been an identified cause or common link, just a description of symptoms, findings and treatment response. However that hasn't stopped many suggestions being put forward (by others) for why I probably have CLIPPERS. So just for the record here they are.

Four Week Journey to Diagnosis

In August 2011 I went into the National Hospital for Neurology and Neurosurgery for a few days of investigations expecting to be diagnosed with Multiple Sclerosis. I was finally let out exactly a month later with a diagnosis of "presumptive CLIPPERS" after MS and lots of other conditions had been considered, investigated and rejected. This simplified account is based on memory and doesn't include the extensive discussions amongst the medical staff on my team which happened behind the scenes and included the detailed results of many more tests than I report here. I've never stayed in hospital before and my experience was that all the medical staff at the NHNN and especially the nurses on John Young Ward were  professional, patient, kind and tolerant sometimes in difficult or unpleasant circumstances.

Something's not right - developing CLIPPERS

Holidaying on the Greek island of Rhodes in May 2011 was the turning point and the end of my pre-CLIPPERS existence (if that doesn't sound too dramatic). Below is a short account of the time between first overt symptoms and being admitted to hospital for investigation.

Double Vision
The week after I got back I was watching television when I noticed that the peripheral vision on my right side was going slightly double. It was worse the further away and the further over to the right I was looking (by moving my eyes not my head). As the doubling was slight and only affected the edge of my vision I wasn't too concerned at first. Also I wear contact lenses for short-sight and get my eyes checked out twice a year so I knew there wasn't anything that got flagged up at my last eye exam. I could watch tv without a problem and get to work OK albeit with that weird feeling that there's something happening in the corner of your eye that you can't quite see.