MRI of CLIPPERS - And Now the Science Bit

CLIPPERS results in lesions with a characteristic appearance, both in terms of where they are and what they look like, on brain MRI. Pittock et al describe them as "a characteristic pattern of punctuate and curvilinear enhancement peppering the pons and extending variably into the medulla, brachim pontis and mid-brain". The lesions are thought to result from some underlying inflammatory process which has yet to be identified. The exact number and location of lesions is different amongst different patients, presumably contributing to the variability in symptoms seen.

To BB Or Not To BB ...

... That Is The Question

During the investigations which resulted in my current diagnosis of "presumptive CLIPPERS" I declined a brain biopsy (BB) (the surgical removal of a brain-tissue sample for laboratory investigation). Here's why.

Life in the Slow Lane

I walk fast, I always have done. In part it's a physical thing as being tall means I need fewer steps to get somewhere than many other folk (I have a higher cadence).  On the other hand natural impatience also plays a part. I don't like to dawdle; I'm a rush-hour train-commuter on a schedule who doesn't like delay. Suffering coordination and balance disorders which impact on walking offers a unique and unwelcome insight into life in the slow lane. Maybe it's payback time for years of commuting intolerance.

If not CLIPPERS then what?

Regular readers will know that a CLIPPERS diagnosis is neither quick nor simple. A large part of the process is excluding other conditions with similar or overlapping symptoms because it is vital that treatment fits the diagnosis as far as possible. Some of these conditions are more amenable to diagnosis than CLIPPERS because they are more common and better understood. The remainder are conditions about which less is known because of their rarity making differential diagnosis even harder. Here are the conditions I have found mentioned in the research literature which have been considered before diagnosing CLIPPERS. I bet that like me, most of you haven't heard of many of these. There are a frightening number of obscure and less obscure things which can go wrong with the old grey (and white) matter. As always please treat my interpretations of these complex disorders with caution and always go to authoritative sources for more information.

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.

Aside on Hospital Life

And now a brief aside from the world of CLIPPERS for some reflections on hospital life. Although I've worked in and around hospitals for much of my career I had never before been admitted to one as a patient. So all of a sudden I found myself as an in-patient for several days of unspecified tests and facing an uncertain outcome. So how did I feel? Bloody marvellous as it turned out.

Four Week Journey to Diagnosis

In August 2011 I went into the National Hospital for Neurology and Neurosurgery for a few days of investigations expecting to be diagnosed with Multiple Sclerosis. I was finally let out exactly a month later with a diagnosis of "presumptive CLIPPERS" after MS and lots of other conditions had been considered, investigated and rejected. This simplified account is based on memory and doesn't include the extensive discussions amongst the medical staff on my team which happened behind the scenes and included the detailed results of many more tests than I report here. I've never stayed in hospital before and my experience was that all the medical staff at the NHNN and especially the nurses on John Young Ward were  professional, patient, kind and tolerant sometimes in difficult or unpleasant circumstances.

In-patient Investigations

Below is a summary in chronological order (as best I can remember) of 3 weeks of in-patient investigations at the National Hospital for Neurology and Neurosurgery in August/September 2011. I'll describe the progression of diagnoses later. Note that most of these tests were either looking for non-CLIPPERS conditions or were to exclude non-CLIPPERS conditions.  Some tests were prompted by findings peculiar to me in other investigations so may not form part of the standard work-up. For comparison I also list the other major investigations reported in the literature for patients being investigated for CLIPPERS. I'm sure there was also lots of variation in the blood and cerebral-spinal fluid tests which I don't have knowledge of. As Sherlock Holmes said:

 "Eliminate all other factors, and the one which remains must be the truth" !