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.

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.

Parallels in this case study.

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.

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.

Steroids - Short-term, medium-term or long-term?

It is now fairly well established in the research literature that for many (most?) people diagnosed with CLIPPERS, high-dose intra-venous corticosteroids (usually Prednisolone) followed by lower-dose orally administered treatment improves the condition. What to do after this initial treatment phase and how to manage the condition in the medium and long term is more debatable. What seems clear, is that some kind of continuing treatment is required. The most common reported variants involve tapering the steroid dose to a low level and then either :

1. maintaining the patient at that dose 
2. maintaing the patient at that dose together with another immuno-suppressant
3. tapering the steroid down to nothing and maintaining on another immuno-suppressant

A new case study discusses these issues in the context of a 63 year old man diagnosed with CLIPPERS. This patient was treated with option 2 above (80mg/day Prednisolone) and then Methotrexate (2.5mg/weekly). However he had complications on Methotrexate and was moved to Azathioprine (100mg/day) and Prednisolone (now 20mg/day). On this treatment, the patient had a good response and no CLIPPERS relapses for 18 months (and onward).

The interesting thing about this paper, is the authors consider the treatment in the context of somewhat related disorders like cerebral vasculitis. There, option 2 is maintained for 2-5 years to prevent relapse, and they suggest a similar treatment strategy may be necessary in CLIPPERS. Now, this week is my 2-year anniversary of first CLIPPERS symptoms and 1-year anniversary of coming off Prednisolone entirely (option 3 above). The authors of this paper also say that successful steroid discontinuation in CLIPPERS has not been reported. My 1-year off-steroid period is too short to be called successful, as others have had relapses after longer periods without Prednisolone. So caution is required, but so far, so good.

Read other articles in this series at Living With CLIPPERS.

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

Another Quick Update

Things have been quiet recently which is why there's not been an update for a little while. Anyone who spent June in the UK will know it's not just because I've been out enjoying the summer sun!

I definitely couldn't do this with double vision ... (Prometheus, IMAX 3D)

I've been pleased to hear from another "CLIPPER" by email this week - that makes at least four since I started writing this blog which shows that CLIPPERS does exist in the real world outside the research papers and is being diagnosed.

I've also been Prednisolone-free for three weeks (but still on Azathioprine). I haven't noticed any change in CLIPPERS symptoms (I don't have any to speak of at the moment thankfully) but have been getting some stiffness in my legs - hips and knees mostly. This doesn't feel neurological in the sense that it isn't like the "locking-up" or balance problems I had last year. It's more like you might feel after you'd run up a steep hill and most noticeable after I've sat down for a long time - could just be middle age creep. I did briefly Google this association with Azathioprine and found some similar (non-CLIPPERS patient) reports. But on the other hand it's the way of the interweb that you can usually find a report of anything you want - if I suddenly developed a wart (or a potato!) that looked like David Cameron I'm sure somebody somewhere will have reported a similar association with Azathioprine. I also found reports of people getting joint/muscle problems when (or even after) coming off Prednisolone although I was a on very slow taper so I don't know if it was that either. Anyway add to the list of things to ask the doc next time I see him, but I obviously don't want to make the mistake of confusing correlation with causation.

I'd also like to thank the slowly growing readership (especially the ones who come back for more!) - hopefully some of the stuff here is still either interesting or useful.

Read other articles in this series at Living With CLIPPERS.

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Slightly Cleaner Than Before

Keeping My Chin Up

Insured At Last  

Well I finally got some travel insurance via All Clear Options but it took a while for their back-office doctors to decide what to do with me. So for the purposes of insurance I now have Primary Cerebral Vasculitis. I spent about a week being investigated for various kinds of vasculitis last year so I guess it makes sense and Wikipedia says it can be confused with Multiple Sclerosis which I was also investigated for. They would only insure me for a single trip and the cost is about 10% of the holiday (well the holiday wasn't that expensive in the first place) which made me do a double-take. A friend who had some more recent completely different (but well known) health problems was quoted about two and a half times the amount I was for a trip which was much further and for longer so I guess it was proportionate. The good thing is I am able to insure my wife as a "Travelling Companion" which sounds a bit Victorian but means she can claim for problems caused by my CLIPPERS too (like cancellation costs etc). Anyway, that's enough about insurance.

Sex and Drugs and Rock'n'Roll (But Mostly Drugs)

Prednisolone is lower than it's been since I started taking it. I'm now well into single figures and moving to 8mg / day tomorrow. Now we find out if the Azathioprine is doing it's job and taking up the slack. If nothing else it's certainly making me paranoid about all the people who's one aim in life seems to be to cough all over me at the moment.

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 Minor Milestone

Apologies to my long-suffering wife - this was actually for a far more important anniversary!

Honourable Discharge?

Today marks 6 months since I was discharged from hospital - hurrah! It seems a long time ago now but shows how things can change quite quickly - up or down. I also just got the follow-up letter from my consultant after last months clinic appointment. No real surprises. Apparently my Lymphocytes are below normal which is (presumably) the expected consequence of the Azathioprine and probably the reason I've been coughing for two weeks - Lymphocytes help fight viral infections. The only other thing of note was that I have a "mild left beating nystagmus" which basically means that I have abnormal eye-movement when looking left. This has been mentioned before and may represent residual damage (to brain - it's not an eye problem). It's not something I notice so I'm not losing any sleep there.

Step On Down

Today also marks another change as I've started stepping down the Prednisolone corticosteroid. The suggested schedule is by 1mg/day/week so I've just gone from 15mg/day to 14mg/day. Some reports have suggested that around 12mg/day may be a crucial dose for some CLIPPERS patients. Last year I briefly went down to 10mg/day and thought I could feel myself slowing down a bit.  At the time, I wasn't on Azathioprine so the theory is that now the Azathioprine provides sufficient immunosuppressant effect to allow reduction and eventual elimination of Prednisolone. We shall see.

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.

Bill's Pills

A brief treatment update. As I'm sure you are bored of hearing by now I am currently on a steady dose of Prednisolone (15mg/day) and an escalating dose of Azathioprine (beginning at 25mg twice daily and aiming for 100mg twice daily)  with the hope that the former will eventually be replaced by the latter.

Three of these = 15mg. They taste bad though. Fruit-juice required.

Over Christmas my escalation plan for Azathioprine hit a minor snag which meant reducing from 75mg back to 50mg. Over the last few weeks my various blood/liver-function tests have been fine so I have been cleared to move back up to the target dose of 100mg. I will presumably stay on this dose or higher for the time being subject to any other problems before we collectively hold our breath and start reducing the Prednisolone. From reading on the web this transfer from Prednisolone to Azathioprine seems a fairly standard strategy in other conditions so there is a reasonable chance it will work ok for me.

One 50mg + 2x25mg = 100mg twice a day.

And apart from that not much to report. Everything fairly normal and certainly stable. I get occasional right-forearm tightness and very slight reduction in walking fluidity (but not so as you would notice) when tired but neither of any real consequence. Apart from that a lingering metallic taste (a bit like paracetamol) which others have reported with Prednisolone. Sleeping has thankfully sorted itself out so I don't usually wake before 6am now. And I seem to have avoided (so far!) the excessive weight-gain and moon-face appearance which is a quite common side-effect of Presnisolone. I have put on about 7 pounds since leaving hospital and do have to be quite careful not to over-eat but that seems to have stabilised too for now.

I have a clinic appointment in about three weeks (in the demyelinating clinic - probably didn't know where else to put me) and probably another scan before then but no date yet. Also keeping an eye on the research literature for new CLIPPERS gems but it's been a bit quiet recently. More news as I get it.

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.

With a Bang or a Whimper?

 

A squawk

My CLIPPERS 2011 ended with more of a whimper - or at least a squawk -  than a bang. On Monday I was booked in at the Day Care Unit at NHNN for an MRI and a meeting with my consultant. On the previous Friday the MRI appointment was pulled forward so I had to be at the unit for 8:45AM. This meant leaving the house earlier than I normally do to get to work! On the first day of my Christmas holiday!! I shouldn't moan too much though - comprehensive monitoring is a good thing.

No, I won't look like Arnold Schwarzeneggar ...

... has been my response to several people when they heard I was taking steroids.

So let's deal with the biggest source of confusion right away.

• Body-builders and people who want to build muscle-mass take anabolic steroids.
• People with inflammatory conditions including CLIPPERS take corticosteroids.

It turns out taking corticosteroids can result in weight gain but mostly as fat around the face, neck and stomach, which would probably make me look even less like Arnold Schwarzneggar. On the plus side I'm unlikely to suffer from "Roid Rage" or testicular atrophy either. Phew.

CLIPPERS Progress Assessment

Just back from 2 days as a guest of the Day Care Unit at the NHNN, at Queen Square. This for reassessment, progress reports and a decision about future treatment options. The background is that I am now in the last week of my decreasing steroid taper but there is growing evidence that CLIPPERS is a chronic condition which must be carefully managed with continued drug treatment to prevent relapse.

Autumnal Queen Square

Treatment - The Next 4 Weeks

Some readers have asked how my treatment has been going since the last update.

October - 40mg/30mg Prednisolone
Things are continuing to improve.  The speech "glitches" have virtually disappeared. The walking coordination glitches have reduced in intensity and frequency and are absent for large portions of the day. I would put my balance/coordination at around 95% of normal. Apart from insomnia, the most obvious (to me) remaining symptoms are the tightness in my right forearm which also locks up further with the walking coordination glitches. Also some intermittent tight feeling across my lower right ribs but this is at the level of discomfort rather than anything worse.

Prednisolone dosing plan

Treatment - The First 5 Weeks

Benchmark

Walking "heel-to-toe" without falling over and without assistance: one step or less.

September 2011 - IV

My treatment began in early September 2011 after over 3 weeks as an in-patient at the NHNN and came as a relief after a much longer that expected period of investigation. I was started on 1g/day of prednisolone delivered intravenously for 5 days for an hour a day. This is a fairly common treatment strategy for CLIPPERS and corticosteroids (like prednisolone) are often used to treat inflammatory disorders in brain and elsewhere. I improved during the IV treatment but not miraculously so. My facial numbness resolved, my walking became more fluid but my slow speech did return to normal. (In fact for a couple of days my speech went into over-drive and I couldn't be shut-up!). There was no change in my double vision and I still had numb fingers and tightness around my midriff. I also developed a tightness in my lower arms, especially on the right side. Additionally I developed "glitches" where my limbs would stiffen and I would walk like a tin-soldier for a few seconds if I was distracted or starting a new activity (e.g. walking somewhere after sitting down for a while). My speech would stall in a similar fashion - the words were queued up and ready to go but I couldn't get them out. These glitches were often accompanied by brief rushes of light-headedness. Over-all though, some modest improvement and a follow-up MRI two days after the end of the IV confirmed reduction in lesion appearance. So I was discharged and continued treatment at home. Note that this was another diagnostic hurdle - no improvement either in symptoms or in MRI would have meant that I wasn't "Responsive to Steroids" and therefore probably not CLIPPERS.