Wednesday, 6 June 2012

Cause and Effect?

Hmmm ...
 Another single CLIPPERS case study has hit the press with free access to the full text too. This one was accepted for publication last October so has been hanging around a bit already. This study raises some interesting questions about the nature of CLIPPERS and in my view - but what do I know? - tries to make itself more interesting than it otherwise might be with unwarranted speculation about a possible cause of CLIPPERS. Also, to my mind this case seems similar but somewhat atypical compared with previous cases (the usual disclaimer about my lack of medical knowledge should  be born in mind).

CLIPPERS or CLIPPERS-like?
The presenting symptoms (right-hand numbness and paresthesia) are not shared with any of Pittock's original cohort of 8 subjects although they are features of some patients later illness (including my own). In addition patients in the Pittock cohort exhibited diplopia either at onset or later on; diplopia is not reported in this case at all. The second issue is the radiological (i.e. MRI) appearance. I work with MRI images a lot but I am not trained to read them for diagnosis. Nevertheless the scans in Figure 1D, 1E and 1F of this new case do not look like the comparable ones for patients 5 thru 8 in Pittock's figure 1. The new case looks to have a single large enhancing lesion but the Pittock cases have multiple smaller lesions centred in the same region but getting smaller and more diffuse further away. Symptoms should roughly correlate with lesion location so the atypical symptoms and lesion appearance may be related.

Now because there is no definitive test or definition of CLIPPERS syndrome it is hard to draw a line in the sand and say one case is CLIPPERS and another isn't if both have had the same possible other disorders excluded. So an important outstanding question is "Is CLIPPERS a well-characterised condition as described by Pittock et al or is it a broader spectrum of disorders than those originally considered?". Hillesheim et al in this new paper describe CLIPPERS as a "diagnosis of exclusion" (which it is currently) but do not provide any discussion about similarities with or differences from previous cases which would have been a more valuable contribution IMHO.

Anyway, I'm not a doctor so this is one for the medics to argue about.

Rant!
The thing that annoyed me more about this case is the association with vaccination. (As those who live in the UK will know we have had our share of vaccination scares in the last few years). To begin with Dr Hillesheim remarks that the patient had the influenza vaccine 2 weeks before first CLIPPERS symptoms; it is quite right that this information should be recorded.

However, he then says that this is the first cases of CLIPPERS "associated with the administration of the influenza vaccine". Now "associated with" is a carefully chosen phrase which doesn't quite mean "caused by" but implies that one is observed together with the other. But let's think about this in another way. How many men over the age of 70 do you think received a flu vaccination last year and didn't get CLIPPERS? I have no idea but I bet it's hundreds of thousands if not millions. So should I write a paper entitled "Influenza vaccination associated with not getting CLIPPERS"? Absolutely not - it's just misleading and unscientific. Or how about this - I was on holiday in Rhodes two weeks before I got symptoms so should possible triggers for CLIPPERS include cheap cocktails, Greek toilets or cramped European flights? Of course not. Or we could ask how many other CLIPPERS cases developed symptoms shortly after vaccination? None that I can recall (but of course let me know if you know different).

Now to be fair, later on the authors list a whole series of rare neurological complications of vaccination so maybe there could theoretically be a basis for CLIPPERS to be considered as a new one. However they state plainly "CLIPPERS is another complication that should be added to this list". What, on the basis of one case, without even any speculation about a mechanism for cause and effect? Again, absolutely not and I can't help thinking the influenza aspect has been promoted from being a small part of the clinical case just to increase publication impact and maybe get some positive press. Finally the authors say that "Vaccination for influenza ... raises the tantalizing possiblity that this may be the triggering event". Well in my own personal case study being conducted in the UK (on myself), "Over-consumption of Greek gin and tonics ... raises the tantalizing possiblity that this may be the triggering event". Unfortunately I won't get a publication out of it.

Rant over - normal service will be resumed shortly.

Read other articles in this series at Living With CLIPPERS.

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