Updates

On Cheddar Gorge in 2022

Time for a few brief updates. Thanks to those who have read the CLIPPERS book and those who left a rating on Amazon; I hope you enjoyed it or found it useful, or both.  You may have read that Amazon are raising their global printing costs in June 2023, but the CLIPPERS book will remain at it's original pricing for now.

I had a telephone review with my consultant recently and, following a brain-scan last year which reported essentially normal (or at least no change), had nothing much to update him with. It's nice to have retained the same consultant through my CLIPPERS journey, which makes catching up easier (for both of us!). We had our now traditional conversation about future treatment strategy. I've been lucky to remain stable on Azathioprine since being weaned off steroids about 9 months after diagnosis. Taking Azathioprine comes with a small hypothetical risk but trying to compare that against the risk of not taking it for CLIPPERS is very hard. My view has always been that CLIPPERS can cause serious and potentially long-lasting problems, which in my case meant a month in hospital and easily six months in recovery; but at least I did recover. The risk of relapse is real but unfortunately unpredictable. Judging by the number of CLIPPERS case reports still appearing, relapse is still common so as before,  I said I thought that relapse was a bigger gamble and my consultant was happy to support that decision.

The fact that I still can't gauge a risk of relapse made me think. I don't have an inside track to the latest knowledge about CLIPPERS, but reading some of the recent papers  makes me feel that in some ways things haven't changed very much. Here's an example from 2023:

"The diagnosis of CLIPPERS is difficult and requires extensive differential diagnosis. A specific biomarker in serum or cerebrospinal fluid (CSF) for this disorder is currently unknown. The pathogenesis of CLIPPERS remains poorly understood and its nosological* position has not yet been established. Whether CLIPPERS represents an independent, genuine new disorder or a syndrome in the course of diseases with heterogeneous aetiology and/or their precursor stages remains debatable and incompletely clarified."

(*nosological = disease classification including an understanding of mechanism)

I accept everything said in this extract, but it could have been written for virtually any CLIPPERS paper over the last ten years. I hope in another ten years a similar extract will read differently.

Read other articles in this series at Living With CLIPPERS.


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Has it really been that long?

Dartmoor 2022 Some rare sun.

You know how it is; there's something at the back of your mind that you feel you really should do but you don't quite get round to doing it. And so when I looked back at this blog page it was a bit of a shock that no new posts have appeared for well over a year. (I'm pretty sure I did a bit of tidying up behind the scenes since then, but it's a poor excuse). I don't have an enormous amount to say, which is why there has been such an update drought, but I did manage to miss my own anniversary of a decade since being diagnosed with (probable) CLIPPERS in 2011. I've partly been prompted to write here after a nice email from a fellow CLIPPERS patient who hoped in passing that the blog silence didn't mean anything bad had happened.

Since the last post I've managed not to catch COVID helped by working almost exclusively from home and by taking every vaccine offered. The booster program is a little random here but they seem to be erring on the side of caution as I've had two initial jabs (Astra-Zeneca) and three Pfizer "boosters". I felt pretty mouldy for a day or so after the second Pfizer one but took more care with hydration and ibuprofen after the third which seemed to help. CLIPPERS symptoms have remained absent and I've now been taking Azathioprine for ten years which is not ideal but probably better than the alternative.

I very recently had my annual neurology appointment in London. It was strange travelling in to the centre on the train for only the third or fourth time in the last couple of years when I used to do the journey most weekdays. My status was reviewed by the same neurologist I saw when I was first diagnosed and I was judged to be stable. There's always the question about whether I want to stop the medication and I ask "what are the risks of relapse and what would be the consequences if I came off it" and no-one really knows; so I stay on the medication as it's kept me well so far.  I'll get another MRI in due course to provide an up-to-date reference in case there are any changes further down the line.

Hopefully it won't be so long before the next post. I hope everyone out there is staying as well as possible.

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CLIPPERS or SLIPPERS?

https://commons.wikimedia.org/wiki/File:Illu_tentorium.jpg

I was recently contacted by someone with a close relative who had been diagnosed with possible "SLIPPERS" syndrome. I initially suspected a typo but then realised that this was a CLIPPERS variant which had passed me by. Initially proposed by Dr Armand in 2015 this condition differs from CLIPPERS in which part of the brain is predominantly affected. In CLIPPERS the enhancing lesions seen in MRI are concentrated below the Tentorium (see image above). In SLIPPERS (Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids) the lesions are concentrated above the Tentorium. The two patients in the original case-study both responded to treatment similarly to CLIPPERS but had presented with seizures and headaches respectively which I think are less common in CLIPPERS. Another patient was subsequently reported by Dr Horng in 2017 who also responded to similar treatment. It's unclear to me whether this is really a distinct syndrome or just a variant of CLIPPERS but at least the treatment response is very similar so the difference for treatment purposes is not crucial (it would seem - I'm not  a doctor).

In other news my medication (Azathioprine) is mysteriously unobtainable in my locale currently for reasons unknown to me. Is it a manufacturing problem, supply problem, hoarding problem? I don't know but it's been suggested I ask my doctor for an alternative - may be easier said than done as, having been stable for quite a few years, changing meds at this stage is not on my agenda. There was a shortage a few years ago which resolved after a few weeks so hopefully the same thing will happen again.

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Some updates

Another critter

A few snippets. First of all, apologies to any forum users who got put off by all the junk that had built up there in the last month or two. I have now cleared this out and will endeavour to keep a better eye on things.

One of the main international sites for rare diseases at the Genetic and Rare Diseases Information Centre has recently updated their page on CLIPPERS. Of potential interest for UK readers, they now list two UK organisations (Encephalitis Society and Brain & Spine Foundation) who may be able to offer support for CLIPPERS.

I'm seeing my neurologist next week for the first time in a while. As usual I'm wondering whether he will suggest any change in treatment. With that in mind, another recent case-report caught my eye as there were similarities to my own experience* and an emphasis on the need for continuing immuno-suppression.  The patient had facial paraesthesia (check), ataxia (check) and diplopia (check) and was treated with intravenous methyl prednisolone for 5 days (check) followed by a steroid taper starting at 60mg/day (check). However other non-steroid medication was not used in addition, and after steroid treatment ceased she relapsed. In the second round of treatment, Azathioprine was introduced during the steroid taper and maintained subsequently; there has been no further relapse for at least two years. So I think I'll be sticking with the Azathioprine.

*Update: Dr Tobin remarks that this case isn't completely typical of CLIPPERS.

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Welcome To 2018

A reminder of warmer times.
It's wall-to-wall rain and sleet currently!

Wow, it's been a long time; in fact I hadn't quite realised how long. 2017 has slipped away with very little fuss. The posts on this blog have been relatively few in the last year which sadly simply reflects that I don't have much to report. My own condition is remaining stable and essentially asymptomatic. My Azathioprine dose has remained at 150mg / day  after being reduced when my doctor got worried about my neutrophil levels. In related good news I have avoided "Aussie" and all other flu variants so far (we are at peak flu season in the UK currently)|. Flu vaccine and careful hygiene, not least as I travel on public transport daily, have done their job.

In terms of wider CLIPPERS news, there is still a trickle of journal papers. The most common topics are case reports on single patients (typically those who don't fit the standard CLIPPERS pattern in some way), proposals for tighter diagnostic guidelines and papers discussing the possible links between lymphoma-type disease and CLIPPERS. I did a quick search and in the last three years the number of full journal papers on CLIPPERS seems quite stable at 4 (2015), 5 (2016) and 6 (2017). (There are likely more short conference papers which are harder to track).

I get the impression, admittedly without much hard evidence, that treatment is becoming more standardised, at least in the acute early phases of CLIPPERS. Managing people like us long-term is more variable, both in the range of treatments available and our collective responses to them! I have a meeting with my consultant in a few months so will pick his brain for any updates from the medical perspective.

Thanks for sticking with the blog and if anyone has any ideas for contents or wants to write an entry, let me know and we'll sort something out.

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CLIPPERS Treatment Strategy Consensus

We had one extra for lunch.

Recently, research papers have appeared from two different groups which both review the published cases to date and suggest treatment strategies. The papers originate from Dr Zalewski and Dr Tobin at the Mayo Clinic and from Dr Taieb's team at Montpellier, both of which have been heavily involved in CLIPPERS reporting and research. It is gratifying to see that there is substantial consensus on treatment which will certainly be helpful for the newly diagnosed.

The first treatment stage is intravenous methylprednisolone 1g / day over 5 days (Dr Taieb suggests up to 10 days if necessary). This should be followed by oral prednisolone 1mg/kg/day (Dr Taieb suggests for a month and Dr Zalewski suggests until expected clinical and radiological i.e. MRI, improvement is seen).

In the second phase Dr Zalewski introduces a "steroid-sparing" agent such as methotrexate or azathioprine or (one I haven't come across before, possibly as it is "15 times more expensive than azathioprine") mycophenolate mofetil. Dr Taieb suggests methotrexate in the first instance; I contacted him to ask why he doesn't use azathioprine (although he does recommend it if methotrexate can't be used for any reason). He pointed out that the reported CLIPPERS cases treated with azathioprine in the literature are far fewer and tend to be atypical. 

The "steroid-sparing" agent is usually ramped up slowly to test tolerance and the oral steroid can then be reduced. Both authors agree that 20mg/day is the minimum steroid dose that should be maintained to prevent symptoms returning until the alternative drug has reached an effective dose level. Dr Taieb also suggests alternative drugs if methotrexate can't be tolerated: azathioprine, cyclophosphamide and hydroxychloroquine.

I have missed out a lot of detail in this summary (and I am not a doctor) but nevertheless these papers do, in my opinion, mark a step towards an accepted treatment strategy which is effective in the majority of cases. Of course this all assumes that an accurate diagnosis of CLIPPERS can be obtained in the first place. If the stage 1 treatment above fails to provide any improvement then the diagnosis is probably incorrect. In addition Dr Taieb suggests that if there is any relapse with oral prednisolone at doses above 20mg/day in conjunction with methotrexate then the case needs to be looked at very carefully again.

P.S. I should mention of course that taking any of these drugs is not without potential problems. So if anyone out there is facing choices over treatment I urge you to ask your doctors about possible side-effects both short-term and long-term so you can make an informed decision.

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Vitamin D

Spring

In the UK we have just moved to British Summer Time, and this weekend Spring has well and truly arrived with mild temperatures and clear skies. Clear skies mean more sun and more skin exposure to sun  means more vitamin D, which apparently most of us Brits are short of. Here are a couple of related things which recently happened together - but are they related? 

Since 2011 I have been on Azathioprine and the main side-effect has been various warts on my fingers of two varieties - the common ones (about 8 at the moment) and so-called periungual warts (present on 7 out of 10 fingers) which appear as dry thickened skin patches down the side of the fingernails which tend to merge together over time. These are apparently a direct result of a suppressed immune system and common when taking this medication. In the last few years I have tried to treat them with duct-tape and with cryotherapy, neither of which were very effective. 

1. In the last four weeks all of the periungual warts have either cleared or significantly reduced and two of the older conventional warts have also gone. I am closely watching the rest.

2. In the last four weeks I started taking daily vitamin D supplements of 10𝞵g (= 400 International  Units) which is the recommended daily dose (at least in the UK). 

So are these two events a happy coincidence or is there a link? Vitamin D is supposed to benefit the immune system, amongst other things; it's role as a treatment for warts (in higher doses) is not proven. On the other hand, my doctor told me a while ago that eventually my immune system would probably figure out how to deal with these warts, but it would likely take several years.

It became more interesting when I started looking into it a bit further and found that there is thought to be a link between low levels of vitamin D and auto-immune disease. However, and this is a BIG, however some studies suggest that these low levels may be a result not a cause, and that taking additional vitamin D could make some auto-immune disease WORSE. The jury is clearly still out (link) and I'm not qualified to comment further. I'll cautiously continue with the vitamin D for now, especially if the warts keep improving.

(Just in case anyone is in any doubt, I am not a doctor and recounting my personal experience, not advocating vitamin D. Anyone considering taking supplements of any kind should always consult with their doctor, especially if already taking other medication.)

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The Alien in the Room

No aliens here.

Wow. It is 5 years since I was diagnosed with (probable) CLIPPERS and pumped full of intravenous Prednisolone for a week. I was still in hospital and waiting for an MRI to show "radiological improvement" before they would let me out. At the time there were considerable question marks, not only about the long-term prognosis for CLIPPERS, but also about whether the diagnosis was correct or whether I might have something potentially worse. Since then, I have made steady progress and been remarkably stable health-wise. But I am careful not to become complacent.

I am a child of the video-game generation and have been playing games of various kinds virtually my whole life. I tend to like games which have a strategic, exploratory and/or puzzle component but am not averse to a bit of (video-game) ultra-violence, especially if combined with one of the above. Currently I am playing a game which I stayed away from for a while as I thought it would be too far outside my comfort-zone - Alien : Isolation. This is a game set in the Alien universe where, to cut a long story short, your character is stranded on a space-station being stalked by a predatory alien and with virtually no effective weapons. You can't kill this creature, you can only hide from it, distract it and occasionally make it retreat for a very short while. The creature wanders the corridors, travels through air-vents and is systematically searching for you. When it finds you, you come to a grisly end. Spooky.

It made me think about my experience with CLIPPERS. Like my character in the game, I know I am trapped in an environment with something nasty which I can't see and can't do much about. In the game, sometimes the alien disappears for a while, sometimes you can hear it rattling around nearby vents and sometimes it comes out of the vents and searches the rooms. In the game I am always listening and looking for signs the alien is near and in real life, although CLIPPERS doesn't seem very close at the moment, I am still looking for signs that it may be lurking nearby. Unlike in the game, if CLIPPERS reappears I can't hide from it, but at least I have a bit more idea what to expect. Also, in the game, I know I will ultimately have a chance to escape completely and I'm hoping the same will one day be true of CLIPPERS.

Update: With Azathioprine reduced to 150mg/day, my white blood cell count has stabilised at 3.4 which is acceptably abnormal. No signs to date that this dose reduction has had any unwanted CLIPPERS effects.

Read other articles in this series at Living With CLIPPERS.

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An interesting treatment case

My local sun-bathing blackbird.

I saw a new case study recently which suggested a variant on treatment. In their paper,

IFN beta 1a as Glucocorticoids-Sparing Therapy in a Patient with CLIPPERS, Dr Rico and colleagues, discuss a CLIPPERS patient who suffered approximately one relapse a year when tapering steroid treatment was used. The initial high-dose treatment gave (incomplete) improvement but once the lower dose treatment ended, the symptoms returned. This patient was first seen in 1996, well before CLIPPERS had been defined as an entity in the medical literature. The doctors suspected an auto-immune disease but had ruled out Multiple Sclerosis (MS) so they decided to try an alternative imuuno-suppressant therapy, namely interferon beta 1a. I don't know anything about this treatment beyond the fact that it has been used to treat MS. The patient subsequently only suffered one relapse every 4 or 5 years and relapses did not permanently worsen his condition.

 

However, the patient was also maintained on a corticosteroid dose equivalent to 25mg Prednisolone every 2 days which makes the interpretation of his improvement less clear. In addition, the authors report that when this corticosteroid was withdrawn a new relapse followed. So it is not clear to me how these two parts of the treatment are working and whether both are required or whether it is the continual low-dose steroid which is important. The authors also repeat an assertion I have read elsewhere, namely that "... except for methotrexate and possibly rituximab, no drug has been able to have sustained control of the disease without combined oral glucocorticoids ...". Maybe I need to put my hand up, as I have been stable on Azathioprine for 4 years after steroids were tapered to zero. Of course, technically I am an IPPER not necessarily a CLIPPER (see previous post) so may be atypical, and there is no guarantee I will stay this way (especially with my currently meandering white blood cell count and treatment changes). Unfortunately, treatment response is just one more part of the CLIPPERS story where there is still a lot of variability and uncertainty.

Read other articles in this series at Living With CLIPPERS.

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Update

Reflection on a London tube-train - curved glass.

Regular readers may recall I was having problems maintaining a reasonable white blood cell count while on 200mg/day Azathioprine. Since then, my readings went up slightly (3.a-little-bit) and then dipped down again to 2.7 at which point the doctors decided action was required. Of course I feel fine day to day but if the white blood cell count gets too low I could be at risk from infections - and this is someone who travels on public transport to work so I'm concious of being exposed to bugs from other people most days. So I was told to reduce my dosage from 100mg AM + 100mg PM to 100mg AM + 50mg PM , a 25% reduction overall. 

I am in uncharted territory now - and a bit paranoid to be honest - as I have been on this dose for 4 years and have no idea what the critical level is or how tightly connected the white blood cell count is to the chance of CLIPPERS relapse. My thinking is that this dose change is simply returning the white blood-cell count to the intended effect of the therapy in the first place so everything should be OK. I have my first blood test since changing the dose this week and I will keep you posted.

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Up and down, like the FTSE 100.

Wormwood Scrubs Common (London)

Well not quite as bad as the FTSE 100 but that's another story (not helped by lots of people on strike and those that aren't on strike going into meltdown over potential Brexit). Of course I'm talking about my meandering white blood cell count which has been wandering a bit further than it should recently.

As my CLIPPERS medication of choice, Azathioprine, willfully interferes with the immune system (which is presumably why it helps keep CLIPPERS at bay), it is expected for my white blood cells to be more thinly populated compared with the norm. The expected range is somewhere between 4 and 7 (I am not a doctor) and mine tends to hover between 3 and 4. About 7 weeks ago it dipped to a historic low of 2.6 and there was much muttering amongst the medics behind closed doors which resulted in me being allowed to stay on Azathioprine for now, but in exchange for having further tests every 3 weeks or so.

On the next test the count had gone back up to 3.something - hurrah! However, on the one I had last week it had dipped back down to 2.9; this is still better than my previous historic low of 2.8. So the tests will continue and I'll let you know if anything strange happens. 

There are no specific symptoms associated with low white blood cells but I was already being as careful as possible to avoid sources of infection - lots of hand-washing and keeping hands away from my mouth, nose, eyes etc. Public transport in the mornings makes me uneasy - too many germs! My doctor emphasised that if I get fevers or unexplained illness I need to see him immediately - presumably under these circumstances I will be able to bypass the 3 week wait for an appointment that is the current situation here.

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Auto-immune or not?

Recent posts have been few and far between - sorry about that. I hope to up the frequency a little now that small details like getting a new job have been resolved.

CLIPPERS has been proposed as an "autoimmune disease", a view supported by the fact that effective treatment is focussed on immune-suppressing agents such as Prednisolone, Methotrexate and Azathioprine. With this in mind, there have been a couple of recent news-items on the nature and treatment of other auto-immune disorders which are interesting.

One concerns a possible future treatment for early Multiple Sclerosis which involves destroying and then regenerating the patient's immune system. In a recent trial, this treatment reduced auto-immune attacks on myelin - the cause of MS - by up to 75%. This therapy is at a very early stage of research but the fact there has been proof of concept in human trials is very exciting. Having said that, the technique as it stands involved aggressive chemotherapy which is not trivial to administer or tolerate. Whether this research results in some general principles which can translate to other auto-immune disorders is unclear at the moment, but worth keeping an eye on for the future.

The other story has been floating around in various forms for several years, but was recently revisited in a British newspaper ("Why a diet of worms could be good for you", The Guardian, February 2016). The essence of this story is that in the past our bodies were used to the presence of parasitic worms and developed a complex relationship with them. Quoting the doctor from the article, "I can give a mouse multiple sclerosis, rheumatoid arthritis or colitis, and when I give it worms, the disease goes away. Can we do that in humans too? I don’t see why not.” Researchers think that parasitic worms adjust the immune system of the host to dampen it down which could have beneficial results when auto-immune disease is present. However the mechanisms are not understood and there have been virtually no studies in humans. Given the choice in a few years time of immune-system destroying chemo or having a few worms to stay, I know which I would choose. However, please note that I am not a doctor and definitely not advocating treating CLIPPERS using worms.

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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.

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CLIPPERS Without Steroids?

One key thing that characterises CLIPPERS is that it responds to steroids in the first instance. So characteristic is this that "Responds to Steroids" is the "RS" in CLIPPERS. Everyone who is treated for CLIPPERS, at some point or another, receives steroid treatment, which for many patients means high-doses of intra-venous Prednisolone.

 

A recent case study (but only a single case) hints that other treatment paths may be possible. I must stress that a single case in a condition that is hard to diagnose like CLIPPERS can't be definitive, but this is interesting none-the-less.

 

This patient had diagnoses first of Multiple Sclerosis and subsequently of neurosarcardosis (both conditions that were considered in my case also). Treatment was with hydroxychloroquine which is an anti-inflammatory used in the treatment of neurosarcoidosis. (Interestingly, the FAQ here, suggests that Prednisolone is the drug of choice for neurosarcoidosis, showing once again that there are many overlapping conditions which can be treated somewhat similarly.) The patient had good resolution of symptoms however, after their symptoms, tests and records were re-examined, the diagnosis was changed to CLIPPERS; the patient has remained well on maintenance doses of hydroxychloroquine since. Also interestingly, Dr Pittock at the Mayo Clinic, had previously tried hydroxychloroquine in one CLIPPERS patient but did not have as good results as in this case study.

 

The authors suggest hydroxychloroquine be considered as an alternative treatment for CLIPPERS because it is well-tolerated by patients, although it is not without side-effects. It will be interesting to see if this study affects treatment decisions in any future patients and whether the good results gained here can be reproduced.

 

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CLIPPERS 2015

A "Happy" meal I had over Christmas

A belated Happy New Year to everyone out there. January 2015 marks the 3-year "anniversary" of when my CLIPPERS symptoms retreated far enough for me to function more or less normally. At the time I was still on tapering Prednisolone and attempting to ramp up Azathioprine while dealing with a few wobbles in various blood tests along the way. I remember book-keeping the changing doses of various drugs needed a certain amount of organisation. There were worries about long-term prospects in 2012 (there still are!) but I have been lucky to be stable on Azathioprine for some time now. 

Although Azathioprine is a common CLIPPERS treatment in conjunction with steroids, I don't recall any cases being reported who have remained stable for this long after the complete removal of steroids. It would be interesting to know if anyone out there is being treated similarly. Am I simply lucky, an anomaly or living on borrowed time? I still occasionally try walking "heel-to-toe", standing on one leg with/without eyes shut etc to try and pick up any early signs of recurring problems. It will be interesting if, as part of their CLIPPERS study, the Mayo team have any comments on my case compared with others.

Finally, a reminder that for those interested in events which raise the profile of rare conditions, the annual Rare Disease Day is coming in February (28th to be precise).

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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.

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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.

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An interesting case study

Swarming Bees in Kent

I recently came across an interesting CLIPPERS case report (Paroxysmal dysarthria and ataxia in chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in which the patient had some experiences in common with mine. I have to be a bit careful as it is very tempting to pick out the bits I relate to while ignoring the bits I don't.

 

Anyway, this patient, a 56 year old man, was treated with 1g Prednisolone / day for three days followed by lower dose oral Prednisolone (30mg / day). The really interesting part is what happened immediately after the high-dose treatment. Quoting from the paper, "... 3 days after the first steroid pulse therapy, the patient presented with paroxysmal exacerbation of dysarthria and paroxysmal limb ataxia". Here, "paroxysmal" means "sudden outburst", dysarthria is speech disturbance and limb ataxia is problems with muscle control of limbs. They go on to say "These attacks lasted several seconds and recurred 20 or more times each day".

 

I have mentioned before, that I had what superficially seems a very similar experience when first treated with high-dose steroids. My problems came when initiating an action (e.g. getting up from the sofa, answering the telephone, crossing the road) and resulted in very restricted "stiff-limbed" motion and inability to talk for several seconds. I had to carefully plan things in advance so I didn't freeze at the wrong moment - especially when crossing the road! Unlike this patient, I had no additional treatment and my episodes gradually reduced in frequency and severity over a few weeks. I don't know if this strikes a chord with anyone else, but it is the first time I remember seeing this effect reported in a paper.

 

I'm currently waiting on a report of a recent "routine" brain-scan - will update when I get it.

 

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CLIPPERS News

 

(Unfortunately the biggest CLIPPERS news this week is not about the neurological condition but about the owner of the American basketball team. I can't compete with that, but can offer a couple of more modest news items. )

I met my neurologist yesterday and, to summarise, "no news is good news". I am being maintained on Azathioprine and will be scanned again in the next few weeks to be on the safe side. Vision (follow-the-finger) was judged good and balance/walking also OK. I'm not brilliant at standing on one leg with my eyes shut but would argue that was also the case before CLIPPERS arrived on the scene!

Last week, I received an update from Dr Tobin at the Mayo Clinic regarding the CLIPPERS repository. As a result of it appearing on this blog, 9 people have signed up so far (including me). Dr Tobin thinks this is an excellent response given the rarity of the condition, and this number of volunteers will allow the team to expand on their originally planned work.

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

Text Book Case?

Autumnal Shrooms

Another CLIPPERS case study has appeared and the interesting thing about it (to my untrained eye) is that there seems to be nothing interesting about it. In fact, if there was a text-book about CLIPPERS, I would go as far as to say it is a text-book case.

In brief, the subject is a 51 year old man who suffered progressive ataxia, diplopia and weakness before being scanned and revealing the characteristic pattern of CLIPPERS-like lesions in the MR images. There is a lot more detail in the article, but essentially treatment was high-dose (1g/day)  IV Prenisolone for 5 days followed by oral Prednisolone tapering down from 60mg/day and  Azathioprine  introduced in parallel to the tapering. This is basically the treatment I received, except I had a slower taper and a few stops and starts with the Azathioprine (because of blips in my blood-work).

This case is reassuring to see in the sense that many of the more recent case studies have either stretched the definition of CLIPPERS or have been complicated by CLIPPERS being diagnosed after, or alongside, other conditions. It is often difficult to get studies published when they are not sufficiently different to what has come before but, as the authors of this study say, "as a recently defined syndrome, any reported case is .... increasing the awareness of this disorder".

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