Blood and Bone

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

Blood

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

Bone

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

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

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.

Being a smart aleck?

smart aleck = someone who is pretentious about their own cleverness

Just For the Record

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

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

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

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

Figure 1

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

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

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

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

Comments for the Author

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

My Response

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

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.

Complicating CLIPPERS

Case Study

Another interesting Case Study appeared last week in the journal Neurology. Unfortunately this paper isn't Open Access but the author, Dr Ortega, was kind enough to send me a copy. The paper describes a 61 year old woman who had a history of Multiple Sclerosis but then went on to develop CLIPPERS. The authors speculate that CLIPPERS was triggered following withdrawal of other MS medication.This is an interesting case but hopefully quite rare. Even so any more CLIPPERS clues are welcome and interactions with other disorders or medications are definitely worth hearing about..

CLIPPERS on the web

I stumbled across my brain on the web the other day - not something that happens every day. It was on the web site of  a private medical practice in the US specialising in dizziness and balance problems. My brain (scan) is on their page about auto-immune brain-disorders. Dr Hain says he's never seen a scan like it in 30 years of practice. I guess I'll take that as a compliment ...

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.

Cutting-Edge Questions and Tedious Jobs

Tedious Jobs

So now all the excitement is over for now it's back to CLIPPERS. Twelve months ago  I was being admitted for investigation at the NHNN with diplopia, ataxia and numb feelings in my hands, arms and feet. Today I spent four hours cleaning the conservatory roof balancing precariously on a step-ladder. This time last year minus a week or so I remember walking up to the local bank and finding it hard to stay on the pavement (it wasn't a narrow pavement). Cleaning the conservatory roof up a ladder definitely wasn't an option then but not being able to see or walk properly now seems a long-time ago. However, I remain vigilant as there's always the chance the symptoms might come back and if they do I want to catch them early. 

    For now though still not much to report. I'm still doing fine on Azathioprine and not expecting the regime to be changed (unless my blood test next week shows anything dubious). 

Cutting Edge Questions

In research-land Drs Keegan and Pittock recently had a short editorial published entitled "Cutting-edge Questions About CLIPPERS". As many of you probably know, Keegan and Pittock were involved in the first scientific papers to recognise and name CLIPPERS as a distinct syndrome. In this short article they advise caution in diagnosing CLIPPERS as the newly reported cases seem to be diverging in their appearance compared with some of the early cases. They also note that even brain biopsy does not give a definitive diagnosis but just excludes other conditions. They urge further work to provide firm diagnostic criteria and monitoring of existing patients so that recurrence can be rapidly treated. All sounds very sensible. I suspect we'll know a lot more in a year or two especially if the rate of diagnosis continues to rise.

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.