Sunday, 21 January 2018

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.

Read other articles in this series at Living With CLIPPERS.

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

Sunday, 22 October 2017

CLIPPERS diagnosis criteria revisited

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.

Read other articles in this series at Living With CLIPPERS.

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

Tuesday, 8 August 2017

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.

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Sunday, 11 June 2017


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.


Read other articles in this series at Living With CLIPPERS.

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