Merry Christmas (sniff)

Sniff

It's not even Christmas yet and I've already received a surprise gift - a heavy Christmas cold. It's always the way, working hard up to the holidays then relaxing a little bit and getting ill. I can't even blame it on the consequences of Azathioprine as this has happened before (and also my wife has been coughing like there's no tomorrow for the last week, so there have been lots of germs floating about). I'd still like to know what role, if any, Azathioprine plays in these kind of infections. I get public transport to work every day, so am presumably exposed to all kinds of bugs, but don't get ill all that often. Should Azathioprine mean I am more frequently ill, or that when I am ill I get it worse or for longer? This is the worst cold I've had for a while but I'm not stuck in bed (some would say I'm a "difficult patient" in that respect) and it's not exceptional on the scale of things. I had another cold about three months ago and got it less severely than my wife. It's all a bit mysterious. Anyway, it won't get in the way of having a good holiday.

So I'd like to wish everyone - the regular readers and those who visit the blog occasionally or stumble across it at random - a very Merry Christmas and hope to see you all in 2013.

Read other articles in this series at Living With CLIPPERS.

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Another Strange Case of CLIPPERS

Now that CLIPPERS has been recognised for a little while the number of new papers simply documenting cases has declined. There is at least some agreement about what constitutes CLIPPERS, even if there isn't a definitive test for it, so reporting new cases isn't, in itself, scientifically interesting. Of course, if the number of reported cases goes up, new research about the epidemiology of CLIPPERS may be required.

 

The new cases that are being reported seem to be unusual or novel in some way. A recent one from Dr Buttmann and colleagues in Germany concerns a 49 year old woman who has symptoms suggestive both of CLIPPERS and primary angiitis of the CNS (PACNS) (otherwise known as cerebral vasculitis, which was a candidate diagnosis for me for a short while). As well as the usual CLIPPERS symptoms this patient also had severe headaches and a seizure as well as other symptoms more associated with cerebral vasculitis than CLIPPERS. Dr Buttmann speculates whether this patient had unusual CLIPPERS, another condition which appeared like CLIPPERS or some combination of both conditions.

I have to say that, from my perspective, although these isolated cases are interesting, what I really want to see is something more detailed about number of reported cases and treatment options and responses in a large population. It is quite possible this information doesn't exist at present. It's a tricky situation as I obviously wouldn't wish CLIPPERS on anyone, or want the number of cases to rise. However, larger scale research may not happen when the number of cases stays small and there are already some treatments available.

Read other articles in this series at Living With CLIPPERS.

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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.

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It's Been A Little While ...

I'm conscious that I haven't updated here for a little while. Been away, been busy and (worst of all), my internet connection at home is currently dead. Anyway a few interesting things to report in the interim. The first was a story in a free newspaper in the UK (Metro) which I wouldn't normally pay too much attention to. However I looked into it and the sources were reputable so here we go. The story is here but I don't know if it will work outside the UK - apologies if not - so I will quickly paraphrase.

Fantastic green moss!

Essentially there has been some recent research looking into ways to "reset" the immune system in people with auto-immune diseases like Multiple Sclerosis. People think CLIPPERS may also be an auto-immune disease (I am not a doctor). The scientists designed artificial "nano-particles" to attach to Myelin  (which is attacked by MS) and essentially distract the immune system. The chief scientist was quoted as saying "The aim was to provide a targeted treatment unlike immunosuppression which weakens the whole immune system." The research paper details are here. Now this has only been tried in mice under very controlled conditions so far, so it is early days. My limited understanding is also that you have to have a very good understanding of the disease mechanism before you can design the appropriate particles - this is something we don't have currently in CLIPPERS. Still, with so few of us, it is encouraging that these kind of generic technologies might one day provide some hope for treatment of a whole range of diseases. 

Interestingly the BBC had another angle about MS recently, which also concerned "resetting" the immune system, this time using an existing drug which has already been licenced for use in other diseases. This kind of low-cost translation of treatments across diseases is also something which can provide at least a modicum of hope to us reluctant members of the CLIPPERS club.

Read other articles in this series at Living With CLIPPERS.

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Out and About

I've been away at a Parkinson's disease conference for a few days. I know (or at least knew) next to nothing about Parkinson's but did some image analysis on one of the featured papers. It was a really interesting meeting even if it was impenetrable to me in places. Parkinson's has been around for a long time - it was characterised by James Parkinson in 1817 - and affects a lot of people, but there is no cure as such, even now, and a limited range of treatments. Listening to the various talks at the meeting it seemed to me that a lot is known in detail about a lot of different aspects of the disease but the full picture is still not understood. Imagine trying to figure out the plot of Lord of the Rings by randomly sampling a few pages at a time from the three books. After you've read 50 sets of pages or so (and if you can put them in the right order) you will have some idea what is going on in certain parts of the story but you will still have a very restricted outlook on the whole; it will take many more pages to reflect the detail and give a true understanding. 

Now CLIPPERS is a relatively new condition (or at least newly identified) but it seems possible (I am not a doctor) that CLIPPERS will fit somewhere into the existing framework of understanding of auto-immune diseases. We already have treatments for CLIPPERS which can alleviate and suppress the symptoms at least some of the time and/or if used early enough. However, as far as I know, no-one has yet figured out the mechanisms, causes or triggers of the disease that will be necessary for a cure. I think the good news is that we are starting from a fairly advanced level of understanding about  related conditions so maybe CLIPPERS will be a missing part of a bigger puzzle ...

Read other articles in this series at Living With CLIPPERS.

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Aside: Contagion

(This is another of those occasional Asides which are only a little about CLIPPERS.)
 

I went for my flu jab last week; I've only started having them since being treated for CLIPPERS so this is only the second. In the UK the good old NHS ensures that as a member of an at-risk population I automatically get an invite to get one for free at my local clinic. So I've had the jab and it was all very straight-forward and no trouble at all. Now I'm wondering what I've been exposed to along the way.

Cover mouth, cough, then wash hands.

I made the appointment and showed up at the clinic. Which was full. Of people coughing - half of them seemed to have flu already even though it was a special flu-jab day. So I checked in and sat down away from the worst of the splutterers. The check-in at my practice is computerised - there is a touch screen and when you arrive you click the relevant brightly-coloured button to select "male" or "female" and your date of birth, after which it identifies you and asks if it has found the right appointment. So far, so good. Perhaps because I got used to it in hospital, I automatically used the handwash next to the screen and sat down for my appointment. I didn't have to wait long, probably 5 minutes or so. However in that time a steady stream of people checked in at the same screen and not one of them used the handwash before or after coughing and touching the screen (or anything else). Given that everyone in the room was in an "at risk of infection" category (about 90% were pensioners and the rest pregnant women) they didn't seem to be taking many precautions. If any one of them had been exposed to Norovirus for instance then this packed room seemed an ideal place to transmit it. Anyway, pretty soon I made it into the injection room and once I'd convinced them I really was supposed to be there (not being elderly or pregnant) the jab itself was barely noticeable.

Next year I'm taking more precautions.

I'm not about to turn into Michael Jackson and wear gloves and a facemask everywhere. Still having had a few bugs in my time and not wanting any more while my immune system is compromised I think I'm entitled to be a bit paranoid.

Read other articles in this series at Living With CLIPPERS.

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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.

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Update: Nothing To See Here.

I left a few loose threads hanging over the summer about blood-test blips, strange aches and pains etc. So here's a quick catch up:

Blood

One of my liver enzymes (ALT) was a bit raised after a previous blood test so another was booked in. That enzyme level was OK the next time but then some other things were off - platelet level (I think) and bilrubin. So another round of tests followed a month later and now everything has settled down to the extent I can move back onto a 3-monthly testing schedule.

Bone

I started having some pains, mostly in my knees and hips after  I came off the steroids. So I agreed to go and have some knee x-rays at the district hospital to check for osteo-arthritis related damage. I felt like a complete fraud as to get there I walked for 10 minutes up an enormous hill with no problem! Anyway the x-rays were reported normal and I have an invitation to see my GP again if I want. I'm going to leave it for now as it's not a big problem and I'm a bit doctored out at the moment.

Drugs

Annual flu jab is all booked in - very important. Apart from that still popping the Azathioprine (100mg twice a day). It's now 4 months since I stopped taking Prednisolone and no sign of CLIPPERS symptoms at the moment. However, I think I'll want to get a year off steroids and symptom-free under my belt before I get too excited.

Read other articles in this series at Living With CLIPPERS.

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People With CLIPPERS to October 2012

I've heard from some more people who have been diagnosed with CLIPPERS and thought you might be interested in a breakdown. (I won't be passing on further details unless told to - have a read of PeopleWithClippers if you want to go public.)

Australia: 1, Belgium 1, Canada: 1, Netherlands: 1,
Spain: 1, USA:3 (+1?), UK: 1 (me!)
= 9 (or 10?) total

So there's a few of us and possibly more who are reading quietly in the background. From what people have told me about their background and symptoms I can see no pattern at all in terms of possible causes or demographics. I would be surprised if anything was that obvious since the doctors involved in the various research papers have presumably gone through patient backgrounds with a fine-toothed comb. Still I hoped something might leap out - never mind, have to wait for the professionals to figure out what is going on.

Read other articles in this series at Living With CLIPPERS.

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Still Talking About CLIPPERS

Dr Keegan gave a talk about CLIPPERS at the National Institute of Health (USA) just over a week ago. From the events calendar:

"For his lecture at NIH, he will discuss Clippers Syndrome and offers the following objectives:
-Identify and treat a chronic inflammatory CNS disease
-Review differential diagnosis of brainstem predominant inflammatory disease
-Add a challenging acronym to neurological differential diagnosis"

This all sounds very interesting. We definitely want to identify and treat CLIPPERS and I'm assuming the third point is to promote CLIPPERS as a possible diagnosis which should be considered more widely. Raising awareness of CLIPPERS within the neurology community  can only be a good thing as presumably, the more cases are found, the more likely research will be done to find definitive causes and treatments.

Read other articles in this series at Living With CLIPPERS.

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First Birthday!

Happy Birthday To Us

Please excuse the slightly length entry - I think I can afford to be a little more verbose than usual to mark a year of blogging.

How It All Began

A year ago this week I was at home, very slowly improving, after nearly 5 weeks in hospital which culminated with a CLIPPERS diagnosis. A combination of high-dose steroids and cabin-fever from being at hospital and home meant I could talk about very little else than CLIPPERS (and boy could I talk). There were also a fair few people who wanted to know what was happening and despite my babbling I was getting bored telling them the same story and answering the same questions. So in an effort to save my marriage (by reducing the babbling burden on my lovely wife) and my sanity (by putting down a definitive account of my illness) LIVINGWITHCLIPPERS was born.

At the time I had no idea if I would persevere with it, not least as the diagnostic uncertainty meant there was a small but finite chance I could be dead by Christmas 2011. However I did gradually get better and the emphasis changed from just focussing on my own problems to providing a digest of what CLIPPERS news I could glean from the web.

Beginnings of a Community

Number of readers of livingwithclippers on a monthly basis

The readership has naturally ebbed and flowed over time and was initially quite high which I attribute to friends and family finding out what the hell had been going on! (When I say "high" I mean up to 20 visits per day - Rupert Murdoch has little competition from me although he has his own problems to deal with.) After Christmas 2011 the visits declined a little but in recent months there has been much more activity. I think there has been a shift towards people who don't know me personally but have some other interest in CLIPPERS for personal (or maybe even professional) reasons. I have also started to receive emails from fellow sufferers (what are we - CLIPPERS?, CLIPPYS?) from Europe, America and Australia.

Whatever their reasons for visiting, the readers of livingwithclippers are a global community as you can see from the map. (No recorded visits from Greenland yet, but I'm working on that.) And let's be quite clear that you have to want to come here. If you just search for CLIPPERS via Google you are highly likely to find other CLIPPERS before you get here: e.g. a popular basketball team, haircare products, boats, tea-bags etc etc Whatever your reasons for visiting, it's seeing the visits rack up week on week which keeps the blog going - there's nothing worse, at least in blog-land, than feeling you're posting straight to a black hole.

The Future

If you're living with CLIPPERS the future is uncertain but there have been some hints in the last year that although the disease is chronic it can often be managed and suppressed, at least in the short-to-medium term. I plan to keep the blog going while there is demand and I have something (hopefully) interesting to say. Maybe a more official support forum will appear at some point but for now you're stuck with my ramblings! But it doesn't all have to come from me. If you have some CLIPPERS news, or a CLIPPERS experience you want to share then send me an email and I'm more than happy to put some guest posts up here. Anyway, thanks for reading and hope to see you next year.

Brecon Beacons, South Wales, Summer 2012

 

 

Read other articles in this series at Living With CLIPPERS.

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September Sun

A CLIPPER on Holiday

Wales

I've been enjoying the last of the Summer sun in South Wales. The day after we arrived we climbed Corn Du and Pen Y Fan in the Brecon Beacons National Park. I looked at my watch and noticed it was exactly one year to the day since I was discharged from the NHNN with a bag full of pills and a diagnosis of presumptive CLIPPERS. My balance had improved after 5 days of IV steroids but was still not great. I also still had double vision and some strange intermittent jerkiness when walking or talking. A fuller account of those times is here. Now I have a smaller bag of pills and the various symptoms are pretty much resolved. From what I can gather I've had a good result from treatment but this is largely down to the luck of being in the right place at the right time and getting a diagnosis relatively quickly. CLIPPERS is tricky to identify and other things need to be excluded, but equally, it doesn't seem to get better by itself and needs treating. I was definitely in slow decline before and during my time in hospital but the pills are working for now.

CLIPPERS News

The debate about possible mechanisms for CLIPPERS continues. A short response to the paper by Dr Ortega (describing CLIPPERS as a complication of Multiple Sclerosis) has recently appeared. I don't pretend to understand the detail of the argument but more discussion about possible causes can only be a good thing and may eventually lead to firmer diagnostic criterion.

Read other articles in this series at Living With CLIPPERS.

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Blood and Bone

My regular blood-testing arm.
I stopped counting how many needles have been stuck in this bad boy a long time ago.

Blood

So the saga of the blood-tests continues. People like me who are on long-term Azathioprine have to have regular blood tests to make sure the "cure" isn't worse than the disease. I've had the occasional blip in a liver enzyme which has settled down for now fortunately. I was hoping to move back to three-monthly tests but a couple of other things to keep an eye on so another panel of tests in a month. Better safe than sorry though. Still taking 100mg twice a day which I think is about as high as it gets.

Bone

I also mentioned in passing that I had some pain in my joints ("Arthralgia" - you learn something every day!), most noticeably in my knees, so I promptly got booked in for some x-rays to check for early osteoarthritis. One or two people on the interweb mention joint/muscle pain in the same breath as Azathioprine, but as I've noted in this blog before, the problem with the interweb is you can usually find someone with any combination of symptoms and possible causes you can think of!

Other than that, pleased to be ticking along. Almost exactly a year ago I was  being wired up for my first 1000mg intravenous dose of Prednisolone after three weeks of investigation in the NHNN and hoping it would do some good. Fortunately it did.

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Being a smart aleck?

smart aleck = someone who is pretentious about their own cleverness

Just For the Record

A couple of months ago I posted an entry here moaning about a CLIPPERS case study which I felt confused cause and effect and made far too much of a supposed link between CLIPPERS and flu vaccination. Anyway I felt strongly enough to write a letter to the journal in question to point out the weaknesses in the paper. Now letters to journals are sent for external review before publication which took a while, but I thought it a good sign that they didn't immediately reject it. In the end they waited for a review to come back ... and then rejected it, which is of course their privilege. As I put several hours work into this letter and because I think I made some legitimate points I've put a copy below for posterity. In the interests of balance, I've also included the reviewer's comments so you can see why they rejected it and my subsequent email to the editor of the journal saying why I thought the reviewer was wrong too. If you work in academia you frequently think reviewers are wrong and sometimes they are, but often it's just  you being a smart aleck ... ;-)

Regarding ”Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids Following Influenza Vaccination” by Hillesheim et al

To the Editor. – The article titled ”Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids Following Influenza Vaccination” by Paul Hillesheim et al (1) reports a new case of CLIPPERS, a recently characterised inflammatory condition of the central nervous system (2). This is an interesting case which adds to the description of CLIPPERS-like disorders but raises questions about the definition and diagnosis of CLIPPERS. The authors also make an unjustified association between CLIPPERS and recent flu vaccination which is not supported by the available data and is potentially misleading.

This case is somewhat atypical; in 19 reported cases to date only 3 others did not suffer diplopia. In addition, the present case does not exhibit the distributed pattern of enhancing punctuate lesions seen previously but has a larger focal lesion within the central pons. The current case is also at the upper end of the reported age range – only one older case has been described, with 13 out of 19 cases aged between 45 and 75 (Figure 1). Clearly though, this case is CLIPPERS-like and could simply represent population variation in a condition which is currently poorly understood.

Figure 1

The connection with influenza vaccination warrants further investigation. Dr Hillesheim associates vaccination with CLIPPERS in the article title but I am of the strong belief that this is misleading and unwarranted. The authors make several statements which are technically true but not defendable in this context. For instance, “… this is the first reported case of CLIPPERS after vaccination” and “vaccination … raises the tantalizing possibility that this may be the triggering event”.  While it is strictly true that the patient was vaccinated shortly before symptom onset, no evidence for a linkage with CLIPPERS is presented and no mechanism is suggested. It is quite right that the vaccination is recorded, but its significance cannot be established from this single case. Finally, the authors list existing neurologic complications of vaccination and state “CLIPPERS is another complication that should be added to this list”. There is no evidence to support this assertion and indeed no other reported CLIPPERS cases have mentioned vaccination. Therefore it is premature to make this connection on the basis of a single case and to link CLIPPERS with vaccination in the article title.

I should declare an interest; I was diagnosed with CLIPPERS in September 2011 and am currently well on tapering Prednisolone and Azathioprine. I am not one of the literature cases. The first and only flu vaccination I received was in November 2011.

1. Hillesheim PB, Parker JR, Parker JC, Jr., Escott E, Berger JR. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids following influenza vaccination. Arch Pathol Lab Med. 2012;136(6):681-5. doi: 10.5858/arpa.2011-0428-CR.

2. Pittock SJ, Debruyne J, Krecke KN, Giannini C, van den Ameele J, De Herdt V, et al. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain. 2010;133:2626-34. doi: 10.1093/brain/awq164.

Comments for the Author

The author does make a valid point in that it cannot be assumed that influenza vaccination directly leads to CLIPPERS; however, I do not believe that Hillesheim et al are implying an absolute cause and effect. They are merely reporting a case of a patient who developed CLIPPERS after receiving the vaccination. With this being such a rare disease with no definitive undeniable cause/trigger or mechanism only associations can be made between the disease and its possible causes, which is what the article is doing, similar to the other reports of CLIPPERS in the literature, until enough cases are reported to find investigable commonalities.

My Response

I still believe Dr Hillesheim over-emphasises the vaccination aspect in his original paper but accept this is a matter of opinion. However as noted in my letter, his statement that CLIPPERS "is another complication ..." (of influenza vaccination) "... which should be added to this list" surely goes too far; however the reviewer disagrees and so  I must defer.

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