Living With CLIPPERS

A Book on CLIPPERS free Kindle-book for a limited period.

noreply@blogger.com (-Bill Crum) — Tue, 06 Jan 2026 14:05:00 +0000

Happy New Year !

From 7th January 2026 to 11th January 2026 the Kindle edition of this book is free on Amazon.

More information and download links on this page:

https://livingwithclippers.blogspot.com/p/a-book-on-clippers.html

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 Book on CLIPPERS is now available.

2025 Update

noreply@blogger.com (-Bill Crum) — Fri, 24 Oct 2025 11:07:00 +0000

On the tourist trail in 2025.

My CLIPPERS journey is the same as ever - take tablets, see Neurologist, occasional brain scan. I am grateful for being stable for so long, whatever the reason.

I updated the References for 2024/2025.

There's an interesting article on this link about Ben, an English chap who was about to start chemo for lymphoma when CLIPPERS was diagnosed. The article claims there are "only 140 recorded cases" worldwide but I suspect 140 cases in the UK (or at least Western Europe) is more realistic? Ben has turned to fundraising and generating music about his experience, and has a YouTube and WebSite to showcase his creations.

A Cautionary Tale

noreply@blogger.com (-Bill Crum) — Wed, 09 Oct 2024 09:14:00 +0000

The blasting of the innocuous-looking spot.

It's thirteen years since I was diagnosed with probable CLIPPERS and like everyone else, I'm ageing, slowly and hopefully gracefully. The skin on my face is increasingly dry and irritated and as someone who is very fair-skinned I know I need to be careful with sun-exposure. Recently I noticed a small but persistent spot on my cheek and eventually decided to get it checked out. The doctor said that she could see I was taking Azathioprine and that my skin wasn't great, but she couldn't see a record of skin-reviews. I said that I was aware I had to be careful with my skin but I had never been invited for a skin-review. So that's how I found myself referred to the dermatology clinic in the local hospital under the NHS rapid referral scheme which is usually used when there is a cancer concern. The doctor said she was almost certain there was nothing serious present, but with my history I should be looked at quickly.

The dermatologist diagnosed various keratoses, told me there was nothing to be concerned about, and then produced a liquid nitrogen gun and froze the original innocuous spot. You can see the evolution of it from almost invisible spot to a blister and then slowly healing skin in the picture. Now there is no sign of it.

I'm taking a few seconds of your time in the hope it will remind anyone on Azathioprine or drugs with similar warnings about sunlight exposure and the need for skin reviews to take them seriously and hopefully head off any unnecessary unpleasantness. Although I slipped through the original monitoring net, at least someone alert picked up on it when I subsequently did have a concern.

A Book on CLIPPERS promotion

noreply@blogger.com (-Bill Crum) — Wed, 04 Oct 2023 13:41:00 +0000

Just a quick update that the ebook edition of "A Book on CLPPERS" will be free worldwide on Amazon from tomorrow (Thursday 5th October 2023) for 5 days.

Updates

noreply@blogger.com (-Bill Crum) — Sat, 24 Jun 2023 14:24:00 +0000

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.

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

Systematic review of CLIPPERS studies

noreply@blogger.com (-Bill Crum) — Sat, 11 Feb 2023 13:23:00 +0000

Wind-battered trees on Brean Down

One of the difficulties in studying conditions like CLIPPERS is their rarity meaning that there are comparatively few cases to draw from. CLIPPERS, with it's variability of symptoms and outcomes and difficulties in concrete diagnosis has additional challenges. However, now that there have been over ten years of scientific publications on CLIPPERS there are opportunities to get a better overview by combining together earlier work. Dr Al-Chalabi and colleagues from the University of Toeldo published a paper in 2022 titled "Clinical characteristics, management, and outcomes of CLIPPERS: A comprehensive systematic review of 140 patients from 100 studies" to try and achieve this. A systematic review is where a collection of previous works are combined following a protocol which strives to ensure quality and minimize bias to hopefully come to stronger conclusions than might be possible looking at the individual studies. In the case of this review, the "clinical characteristics, treatment strategies and outcomes" of CLIPPERS were assessed.

My reading of the review is that the authors drew together some common themes from the individual studies but that the amount of variability and uncertainty still hindered their ability to draw firm conclusions, even in over 100 nominal CLIPPERS patients. They found 60% of their cohort were male and the mean age of onset was 46 years (which is very close to the age I first got symptoms). The most common (but not the only) symptoms, in order, were ataxia , diplopia, and dysarthria; my own experience was diplopia first, then quite quickly followed by ataxia, and latterly by some dysarthria just as I began treatment. They also found that around 15% of the patients studies had some form of malignancy which presumably means CLIPPERS wasn't their ultimate diagnosis (but I am not a doctor). In terms of long-term treatment, Azathioprine and Methotrexate, were the most common, but not the only, drugs.

The authors also report that a shorter time on steroids was associated with an increased risk of CLIPPERS relapse which, to me, is the most interesting of their conclusions, possibly, and very unscientifically and with no evidence, because I have long had a gut feeling that longer steroid tapers might be better. The authors suggest that, going forward, steroid tapers should be very slow, although they don't state what "slow" means - presumably months?

These studies are important and as well as making the most of previous studies can hopefully direct future research.

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 Book on CLIPPERS : The Paperback

noreply@blogger.com (-Bill Crum) — Fri, 13 Jan 2023 11:48:00 +0000

The paperback version of the CLIPPERS book is now available* as per the links on the last post and in the A Book on CLIPPERS tab on the main Living With CLIPPERS website.

*for some reason the Amazon India marketplace does not offer printed books via Kindle Direct Publishing

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.

Living With CLIPPERS : The eBook

noreply@blogger.com (-Bill Crum) — Fri, 06 Jan 2023 14:48:00 +0000

Happy New Year!

I thought I'd begin 2023 by fulfilling a minor promise to myself to consolidate the stuff that's been accumulating on this blog over the last decade or so into a more digestible and permanent form. The resulting ebook "A Book on CLIPPERS" focuses on my experience with CLIPPERS from first symptoms through to diagnosis, treatment and recovery. It also has sections on what is known about CLIPPERS and the key research issues, at least as far as I understand them. The difference between the ebook and the blog is that the ebook is written more as a narrative with events in the order they happened and with less of the "fluff" or more speculative stuff that occasionally cluttered things up on-line. It's even been proof-read!

"A Book on CLIPPERS" is available world-wide via Amazon's Kindle store. Kindle ebooks can be read on a Kindle device, or any computer or phone for which a Kindle app is available (which is most of them). It is free to members of Kindle Unlimited and otherwise almost free (around 1 USD / 1 GBP / 1 EUR or similar). I am investigating the possibility of a physical paperback edition through the same platform and will update on that in due course. I've included some links to the store-page in different marketplaces at the bottom of this post.

Here's the blurb:

What’s it like being diagnosed with a brain condition so new and rare that even the doctors treating you have never heard of it, much less treated any other cases? CLIPPERS (Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids) was first identified in 2010 in a handful of patients in the USA and Europe. This book tells my story from the first seemingly innocuous symptoms in 2011, followed by hospitalisation on a neurological ward, and eventually to diagnosis, treatment, and recovery.

In this honest account you'll learn about:

how CLIPPERS symptoms can quickly escalate from a minor inconvenience to a major problem
how a mystery condition is investigated and diagnosed at a leading UK hospital
the most common CLIPPERS symptoms and treatments
the challenges of CLIPPERS diagnosis
important issues and outstanding questions about CLIPPERS

This book provides a resource about the experience and treatment of CLIPPERS, as well as pointers to the most important research over the last decade. I hope it will inform and inspire both those directly affected by CLIPPERS and anyone else who is interested in rare diseases.

Here are the links to the ebook:

(US) https://www.amazon.com/dp/B0BRQS83K6

(UK) https://www.amazon.co.uk/dp/B0BRQS83K6

(DE) https://www.amazon.de/dp/B0BRQS83K6
(FR) https://www.amazon.fr/dp/B0BRQS83K6

(ES) https://www.amazon.es/dp/B0BRQS83K6

(IT) https://www.amazon.it/dp/B0BRQS83K6

(NL) https://www.amazon.nl/dp/B0BRQS83K6

(JP) https://www.amazon.co.jp/dp/B0BRQS83K6

(BR) https://www.amazon.com.br/dp/B0BRQS83K6

(CA) https://www.amazon.ca/dp/B0BRQS83K6

(MX) https://www.amazon.com.mx/dp/B0BRQS83K6

(AU) https://www.amazon.com.au/dp/B0BRQS83K6

(IN) https://www.amazon.in/dp/B0BRQS83K6

Read other articles in this series at Living With CLIPPERS.

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Has it really been that long?

noreply@blogger.com (-Bill Crum) — Wed, 25 May 2022 14:47:00 +0000

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.

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.

Light at the End of the Tunnel?

noreply@blogger.com (-Bill Crum) — Thu, 31 Dec 2020 14:22:00 +0000

The gaps between posts are getting gradually longer and I have little excuse as I've been at home since March save for a brief, COVID-secure, sojourn to Dorset (UK, South Coast) in September. Fortunately my day-job is intact for the moment and I've avoided COVID (except possibly last Easter - see previous post). So now in the UK we are fortunate to have a vaccine roll-out in progress although who gets which vaccine and when is hard to predict. Broadly speaking, the elderly and those who look after them in a care-setting are high up the list. I haven't been contacted to get a jab yet - the so-called "clinically extremely vulnerable" are in the fourth priority group of nine in recent advice which I notice has just been withdrawn. (In case there is any doubt, yes I will be getting the vaccine at the earliest opportunity.)

Hot off the press is some updated advice to the UK government on vaccine priorities. The full document is here: advice on priority groups for COVID-19 vaccination, 30 December 2020. Some interesting extracts for "clinically extremely vulnerable" people i.e. including CLIPPERS patients being treated with steroids and/or steroid-sparing immunosuppressants include:

"the overall risk of mortality for clinically extremely vulnerable younger adults is estimated to be roughly the same as the risk to persons aged 70 to 74 years"

"Many individuals who are clinically extremely vulnerable will have some degree of immunosuppression or be immunocompromised and may not respond as well to the vaccine. Therefore, those who are clinically extremely vulnerable should continue to follow government advice on reducing their risk of infection."

"Consideration has been given to vaccination of household contacts of immunosuppressed individuals ..." (but until evidence is accrued ) "... the committee is not in a position to advise vaccination solely on the basis of indirect protection."

"Once sufficient evidence becomes available the committee will consider options for a cocooning strategy for immunosuppressed individuals, including whether any specific vaccine is preferred in this population."

So it sounds like the case for vaccinating immuno-suppressed people early is being strengthened and they are considering whether to also vaccinate other members of those households if there is evidence that the vaccines also reduce transmission. They also don't know which vaccine if any is a better fit for vulnerable groups. So no magic bullets yet and of course the UK government does not have a brilliant record for "following the science" whatever they may say publicly. Fingers-crossed for 2021.

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.

Life in Lockdown

noreply@blogger.com (-Bill Crum) — Sun, 28 Jun 2020 13:00:00 +0000

The daily "commute"

The UK is emerging from coronavirus lockdown - too soon? - and as one of the "clinically highly vulnerable" due to immunosuppression I have been advised (the UK government *advises* the vulnerable rather than instructing them) not to even leave the house for the last 3 months. Having carried out my own risk assessment I decided that it was better for my sanity and physical well-being to take a daily walk around the nearby park and field. Some days a bit of planning is required to avoid dog-walkers but going before work (I'm working at home) means there's very few folk about. So far so good and a world away from my usual two-train journey into and across London. Whether I ever go back to that commute is a discussion for another day, but work are currently saying we shouldn't expect to be back in the office this side of Christmas - I won't argue with that.

The future is a bit less certain for us "shielders" as we continue to be at risk with the virus in circulation. The big question is how much risk? I may be classed as vulnerable but I am not unwell or unfit so who knows how I would deal with COVID? An effective vaccine may be the only way to get some certainty while the virus is still around. There are many teams working on different kinds of vaccines including a trial currently in it's early stages at Imperial College in London. Vaccines which rely on live virus (not the IC one) may not be suitable for people like me despite their likelihood of being most effective. For the time being it's a case of keeping my head down until the picture is clearer.

Like many others in the UK I've had a couple of bad viruses this year already. One was cold-like and knocked me out for two weeks plus at Christmas. I had another around Easter - not sure how I caught that! - which was more sore-throat and cough. No temperature on either occasion but had some episodes of breathlessness including one particular evening at Easter where my heart was pounding and I couldn't get to the kitchen and back without panting. Were either of those COVID - I've no idea but they weren't classic symptoms and I wasn't tested. When they get the antibody tests sorted out I will try and get tested just to see .... in any case it currently isn't known whether a positive antibody response guarantees resistance. We continue to live in interesting times. Stay safe!

Read other articles in this series at Living With CLIPPERS.

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Did something happen?

noreply@blogger.com (-Bill Crum) — Sat, 14 Mar 2020 16:22:00 +0000

It's a thumbs up from me

It's been longer than I thought since I last wrote something here. This reflects that in my life, as far as CLIPPERS goes, not much has changed. Still taking the tablets, still deciding in conjunction with my neurologist to keep taking the tablets, still wondering if I will always be taking the tablets.

But probably for me and everyone else reading this blog, something has changed. The emergence of SARS-CoV-2 (the virus) and COVID-19 (the illness) looks like it will affect most people in some way even if they don't catch it. I'm not going to speculate wildly about COVID-19 but one thing I know: people with compromised immune systems are more at risk and I am one of those people. Actually maybe I know more than one thing; my understanding is that people like me are not more likely to catch it, so we can take steps to reduce our exposure, and we not certain to have a more serious illness - it's all about risk. Still, I don't like playing games where the odds are biased against me and this seems like one of those situations.

I had already been mulling whether to work from home more (I'm lucky because I can) and at what point I should do this. I travel to work on several different kinds of public transport, which are often busy, in a city with rising numbers of cases, and the government estimates there may be up to 10 times more cases than they know about. My employer has been proactive though and issued a statement yesterday saying that anyone classed as vulnerable by Public Health England should work at home from now on. So that decision has been taken out of my hands and I feel relieved if somewhat daunted at the prospect of being at home for several months.

There are lot's of unknowns still. The UK government is in a "delay" phase of managing COVID-19. Paraphrased this means: (i) "we can't stop it spreading, so we will slow the spread so as not to overwhelm the health services" (ii) "we will protect the vulnerable in the hope that enough other people build up resistance to stop it spreading further". Whether or not (ii) will be effective is the big question. All we can do is keep calm and carry on. And wash our hands relentlessly.

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 or SLIPPERS?

noreply@blogger.com (-Bill Crum) — Sat, 28 Sep 2019 16:06:00 +0000

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.

Read other articles in this series at Living With CLIPPERS.

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2019 Update

noreply@blogger.com (-Bill Crum) — Sat, 06 Apr 2019 10:13:00 +0000

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.

Autumn already

noreply@blogger.com (-Bill Crum) — Sat, 20 Oct 2018 15:02:00 +0000

A red pineapple plant.

Doesn't time fly? It's been six months since my last proper update and since then a very hot summer (by UK standards, 30C+) has been and gone and Brexit looms nearer. It's been hard to add interesting content to this blog recently. There are still new research papers on CLIPPERS appearing and I add them to the CLIPPERS Research Papers page when I get a chance. However, the majority seem to be quite niche and/or too specialised for me to understand to any extent. In addition I don't have any personal medical developments to report - just a vague feeling I've been taking Azathioprine too long (nearly 7 years) but not ready to try coming off it yet. We need more data!

Perhaps the most important new research is in cases of CLIPPERS in children. Two recent papers discuss this issue. The first from Mario Sa et al in the UK present three case studies of children diagnosed with CLIPPERS all of which had a poor outcome. They suggest that CLIPPERS may be a more aggressive and harder to treat condition in children. However in the second paper, Dr Tobin suggests that the three cases don't meet current diagnostic criteria for CLIPPERS (although they have a lot of shared characteristics). I have commented before on how this diagnostic uncertainty in CLIPPERS comes up again and again and, although the situation is slowly improving, it would be a real advance to strengthen the diagnostic tests.

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.

Some updates

noreply@blogger.com (-Bill Crum) — Sat, 14 Apr 2018 15:37:00 +0000

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.

Read other articles in this series at Living With CLIPPERS.

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Welcome To 2018

noreply@blogger.com (-Bill Crum) — Sun, 21 Jan 2018 16:23:00 +0000

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.

Read other articles in this series at Living With CLIPPERS.

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CLIPPERS diagnosis criteria revisited

noreply@blogger.com (-Bill Crum) — Sun, 22 Oct 2017 14:35:00 +0000

Autumn mushrooms

The Mayo team have been busy as another interesting paper has appeared which really emphasises the continuing problems of diagnosis in CLIPPERS.

In the paper they perform a detailed comparison of 35 patients who had symptoms suggestive of CLIPPERS. (This blog gets a credit in the text as a patient advocacy site which helped connect some of the subjects with the Mayo). After re-assessment including detailed consideration of imaging and response to steroids, CLIPPERS was confirmed in 23 of the patients. One of the most striking results is that when the differences between the CLIPPERS and non-CLIPPERS groups were analysed, there were no significant differences in terms of symptoms commonly associated with CLIPPERS (e.g. gait ataxia, diplopia, dysarthria etc) or in terms of pre-existing cancers or smoking status.

There is a lot of detail on the cases here which leads the authors to suggest a distinction between CLIPPERS cases: "probable" CLIPPERS for patients who fit all criteria but didn't have brain tissue biopsy and "definite" CLIPPERS for patients who fit all criteria but also had brain tissue biopsy with supportive findings. Unlike the paper from Dr Taieb's group I talked about in June, there is no focus here on the relapsing nature of the disease.

A revised set of diagnostic criteria is presented which includes some statements on neuropathology (i.e. tissue analysis). Interestingly both the clinical presentation and neuropathological criteria include the requirement "no better explanation" which emphasises that CLIPPERS is still regarded as somewhat of a "last resort" diagnosis.

On a slightly more optimistic note, I am now over 6 years since being discharged from hospital with a bag full of drugs, double vision and problems walking straight. The diagnosis was "probable" CLIPPERS and the outlook was distinctly uncertain. The outlook is still not exactly clear but everything else is pretty good.

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CLIPPERS Treatment Strategy Consensus

noreply@blogger.com (-Bill Crum) — Tue, 08 Aug 2017 10:09:00 +0000

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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CPPERS, PPERS, LIPPERS or CLIPPERS?

noreply@blogger.com (-Bill Crum) — Sun, 11 Jun 2017 11:27:00 +0000

There's a storm coming ...

A very interesting paper has recently appeared by Dr Taieb and colleagues about treatment strategies in CLIPPERS. I will return to this theme in a subsequent post but wanted to focus on something more basic, namely whether CLIPPERS is a single condition. In this recent works which reviews the majority of previously published cases, Dr Taieb proposes some division of CLIPPERS into sub-types. My reading of this is that it is a sub-division of convenience based on symptoms, investigations and response to treatment rather than any new insight into underlying biology. Nevertheless, it has been apparent for some time that there is immense variability under the CLIPPERS "umbrella".

Dr Taieb lists 5 key features of CLIPPERS which I paraphrase more simply here: (i) characteristic signs and symptoms, (ii) characteristic pattern of lesions seen in MRI, (iii) prompt response to steroid treatment, (iv) no competing diagnosis, (v) characteristic appearance of brain biopsy. So as a reminder, CLIPPERS stands for "Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids". With this in mind, Dr Taieb suggests that sufferers with a single attack and the first 4 or 5 key features are "PPERS" or "LIPPERS" respectively and sufferers with more than one attack and the first 4 or 5 key features are "CPPERS" or "CLIPPERS" respectively.

I think the key interpretation of this system is that it is designed to reflect the available evidence about each case and make comparing cases easier. However it is influenced by the range of tests done (i.e. not everyone has brain biopsy) and the success of treatment. For instance, to date I have had a single attack and I declined a brain biopsy so I have the first 4 features and am "PPERS", but this can't distinguish between someone who has successful treatment and someone who simply has a disease that doesn't relapse.

In the diagnosis of Multiple Sclerosis, one of the criteria is that damage must have occurred at two different times - it is an inherently relapsing disease. However, presumably this is only true while effective treatments which could be given after a single episode are not available. I think the same is true of CLIPPERS and that when treatment strategies improve, the role of the "relapse" in diagnosis may dwindle.

(NOT A DOCTOR)

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Vitamin D

noreply@blogger.com (-Bill Crum) — Sun, 02 Apr 2017 14:10:00 +0000

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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Parallels in this case study.

noreply@blogger.com (-Bill Crum) — Tue, 17 Jan 2017 15:55:00 +0000

Making bread while I wait for more CLIPPERS news.

Happy New Year - it's been a while. I'm afraid everything has been a bit quiet recently.

Anyway, new year, new post, new case-study. When I finally got around to reading this paper I was pleasantly surprised for two reasons. First, if you have been hanging around here for a while and caught up with some of the jargon, it has a quite concise review of the state of CLIPPERS knowledge in 2016. Second, the treatment strategy is more like my own experience than most of the other reports out there.

In this study a 46 year-old woman first had problems with horizontal eye movement . She had dizziness and problems with gait which developed over 4 months. So this lady was eventually treated with high-dose Prednisolone (in fact in three phases of 500mg/day, 250mg/day and 120mg/day over 3 weeks in total) followed by tapering oral steroids which resulted in very good improvement of symptoms. The patient remained stable on Azathioprine (which was introduced while still on Prednisolone) for at least 6 months - i.e. the length of time reported in the paper. This is far too short a time-period in CLIPPERS to be very significant but encouraging nonetheless. The authors note that treatment with Azathioprine is rarely reported but they consider it important (and I agree) to investigate drugs which may work in the absence of corticosteroids, at least in some patients.

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A neurologist calls ...

noreply@blogger.com (-Bill Crum) — Sat, 19 Nov 2016 16:40:00 +0000

The greenest caterpillar I ever saw!

... or rather, I call on a neurologist.

Last week was my first (and likely only) appointment this year with my neurologist who has been managing my care since I was diagnosed in 2011. Since I last saw him my drug regime changed slightly due to some worries about blood tests. My understanding was that my total white cell count was dropping too low which would make me susceptible to infection.

My neurologist clarified this by explaining that there are several different types of cells in the total. The one which was causing concern in my case was the neutrophil count. The web tells me that neutrophils fight infection and if there are too few of them even bacteria normally found in the mouth, on the skin and in the stomach can cause serious problems. Now the drug (Azathioprine) I take for CLIPPERS aims to reduce the lymphocyte count - lymphocytes are the cells associated with CLIPPERS. But clearly for whatever reason, both cell counts were being driven down over the summer. He was reassured by my more recent test results and my Azathioprine dose is high enough (based on body weight) to still be having an effect on lymphocytes. We did the usual eye-tracking and finger-pointing tests and some checks on muscle-tone and reflexes and nothing cropped up there.

We also had a discussion about long term Azathioprine use. Unfortunately we don't know for sure if that is what is keeping me well. I said that if the risks of serious illness associated with taking Azathioprine long-term were low then I felt I had more to lose if I stopped taking it and suffered a CLIPPERS relapse. He said he agreed but it was hard to be definitive because of the lack of knowledge about how CLIPPERS works. So I said I would keep taking the tablets.

It is also sobering when reminded that my status is "in remission from cerebellar disease" which sounds like I am stuck in some kind of waiting room.

Read other articles in this series at Living With CLIPPERS.

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The Alien in the Room

noreply@blogger.com (-Bill Crum) — Fri, 02 Sep 2016 13:43:00 +0000

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.

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An interesting treatment case

noreply@blogger.com (-Bill Crum) — Sun, 10 Jul 2016 17:54:00 +0000

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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