To B, or not to B: that is the question:

Here's a pretty picture of  cells of our immune system:

First time I had an introduction to how this worked was at Cardiff in 1988. Our immune systems are truly amazing (and just a little more complex than the picture above). But I had no idea that the monoclonal antibody breakthrough at that time was being led by rituximab, (subsequently approved for use in 1997) and even less idea of the future relevance to myself. Here is the lovely Prof Steven Hauser from the US explaining the story:

https://www.youtube.com/watch?v=g83lKeSWJtc

Please bear with it (if you can spare a few minutes), he speaks clearly and and even John followed the first bit. You might want to give up after that (John fell asleep) but for me it was one of the best explanations of MS I've ever seen and how far we have come with treatments. To sum it up, MS is a B cell led disease.

Yes, T cells follow after them, join the party and cause great annoyance to the resident microglia (monocytes that settle in the brain) but the B cells started it. And we know that the memory B cell is to blame:

http://www.ebiomedicine.com/article/S2352-3964(17)30045-2/pdf

Fast forward 30 years and rituximab is at long last being used (off-label) to treat MS. Unfortunately it's too expensive for the NHS to permit off-label use. Why off-label? It was never commercially viable for Genentech (now Roche) to bother with MS clinical trials as remaining patent life expired in 2013 (Europe) and 2016 (US). So it's brother ocrelizumab ('Ocrevus') is now licensed in the US but we're still waiting in Europe. And then NICE will have to approve. I only stand any hope of receiving it if my recent MRI shows evidence of activity, allowing my kind neuro to add the magic word 'active' in front of my secondary progressive diagnosis.

But why would I want ocrelizumab when I can have off-label cladribine injections?

16 tandems and 3 solos...

...ride from Glastonbury to Castle Cary for lunch on a beautiful autumnal Sunday.
30 mile return trip.

With my good pal and fellow MSer Kate. No, we didn’t cycle on the same tandem, that would be a disaster! Tandems are great for getting exercise with MS, our husbands balance for us! And yes, we do pedal on the back 😉

Investigations and the T-shirt to prove it

We went to London and I...

1. Had an MRI

Five years (almost to the day) since my last one and nearly 12 years since my first, time to find out the state of play in my brain. MS is likely to be still 'active' i.e. lymphocytes still breaking through into my brain to wreak havoc periodically as I'm worsening quite fast i.e. probably still having relapses. As my previous neuro pointed out to me two years ago 'I don't need an MRI to tell me that'. I'm sure he was right too. Is that still the case today? One thing for sure, the MRI scanner never lies. This time it had a chance to catch errant lymphocytes in action, thanks to a gadolinium contrast medium, something like this:

for the benefit of any chemists 

Maybe I'll have some Gd lurking in my brain forever more, to be honest, that's the least of my worries. In case there was nothing to catch at that moment in time, the scan also picks up the usual evidence of any new damage since 2012.

2. Had a lumbar puncture (LP)

https://www.mstrust.org.uk/a-z/lumbar-puncture

First time I've had the pleasure. Actually, it wasn't anything like as painful as I'd heard. Which was just as well, as the whole procedure took rather a long time. About an hour and a half. For no reason in particular I understand, the Dr could not get his needle to tap into my CSF. As a result my lumbar spine now has a pattern of join the dots along it. Everyone in the room was super-nice and I always enjoy having a medical student present as I get to benefit from the explanation and teaching for free! So I learned that an 'atraumatic' needle (by inference suggesting a 'traumatic' needle is the alternative?) is used. Atraumatic needles are much less likely to result in headache and lo and behold, no headache. Dr also kept topping me up with local anaesthetic as the procedure was taking so long, so it wasn't until I was on the train home later that I started to feel a bit sorry for myself. 

What will this show? At Barts everyone has an LP to establish two things at treatment baseline: 

a) Oligoclonal bands (OCBs)

This are formed in the CSF due to the presence of antibodies. Often done to diagnose MS, especially if MRI inconclusive. Hence this LP was my first (my MRI in 2006 showed multiple lesions 'disseminated in space' and I'd had relapses 'disseminated in time' all sufficient to diagnose MS).

b) Neurofilament levels (nfls)

Neurofilaments are cytoskeleton proteins (scaffolding) that support the axons in the spinal cord. I've never considered this idea (before learning about it on the Barts blog), but without neurofilaments the axons would be suspended in mid air. In MS, axons die and neurofilaments break off into the CSF. So, nfls are a biomarker of disease progression. 

3. Met some famous people and got the T-shirt to prove it!

Mouse Doctor,  Mouse Doctor2 and Dr K. Fantastic to meet these wonderful people for real at last. I am indebted to them all for years of dedication to MS research. Such lovely people too.

Dr K is leading on the proposed CHARIOT-MS trial studying cladribine for people with advanced MS. That's people like me, who don't qualify for any treatment according to the powers that be NHS England. If CHARIOT goes ahead the trial will be available at centres across the UK. 

https://www.youtube.com/watch?v=4pKmpCP4hCY

Nous sommes allés à La Rochelle avec G-PCAT...

...which unfortunately meant it wasn't possible to bring Charlotte and we had to hire this heap of uncomfortable junk:

A miracle we made it over le Pont de Ré and back at all. Well worth the effort, Ile-de-Ré is beautiful. Next year we travel Easyjet and check Charlotte in too! 

It was an exhausting holiday, climbing in and out of the aircraft is becoming a challenge. The Easyjet option is looking extremely attractive. À bientôt!

Annonie Mouse goes camping

Ok, so the large family tent was all there ready for us fully equipped including proper beds, duvets and pillows. That's not camping laughed daughter Louise  (probably having spent the weekend wild camping somewhere next to a remote Scottish loch). In our defence, note the absence of car next to the tent. Taking a car to Guernsey is completely unnecessary, nowhere is far and bikes (and tandems) are free on the ferry :-) Enjoyed a wonderful sunny weekend with lots of swimming in the waves, seafood and hedge veg  (Guernsey thing, veg/fruit/eggs etc for sale by roadside). Last time for staying at this site though, loos are a million miles from tent (ok probably 100m) and it's just too far to walk there and back when tired. As for the showers, they were even further so didn't happen. Bathing in seawater for four days didn't do me (or my hair) any harm ;-)

#ThinkHand #Chariot-MS

Is being unable to walk so bad? 

Hannah Cockroft, 3x Gold, Team GB Rio 2016

I don't know, is the truthful answer, as I can still walk. A bit.

I've always thought of people as either being able to walk or not i.e be ambulant or wheelchair-bound. In reality, if not born wheelchair-reliant, abrupt transition to using a wheelchair all the time only happens with things like (for example, not exhaustive list) physical injury, stroke or MS relapse. Progressive (worsening over weeks, months, years) MS is by nature a gradual process as nerve axons die and neuronal reserve  (alternative pathways) is lost.

Two years ago I was managing to walk up Glastonbury Tor every weekend. It was getting harder. Then the walk to work with climb up stairs when I arrived became a challenge. Early last year I got caught out at a craft fair, just being on my feet milling around caused me to look round frantically for a seat after 20 minutes.

And now I am a wheelchair user. Sometimes. But not always, or often even, thanks to Charlotte and Harriet. I am grateful for the privilege of gradual easing-in to wheeled travel I view my chair as welcome rest and am always relieved to be able to sit in it. My heart goes out to those who find themselves having to deal with the enormous psychological adjustment needed to be suddenly wheelchair-bound. I will get there too, one day, but I have time to mentally prepare and deal with it.

But what about use of my upper limbs? Now that I feel more strongly about. I do everything with my hands after all and cannot imagine being without them!

Two brilliant initiatives by the team at Barts MS are the Think Hand campaign to raise awareness of this issue and the proposed ChariotMS clinical trial of generic cladribine (that drug again) for people in wheelchairs. Incredibly, to date, people with more advanced MS have always been excluded from drug trials and even when people with progressive (gradually worsening) MS have been included the results never appear great due to the dogma of using walking as the outcome measure.


https://www.youtube.com/watch?v=BrIShODY83g&feature=youtu.be

It's better by bike

Why is it easier to pedal than walk?

We've just enjoyed another trip with our tandem, this time in Fort William in the Highlands of Scotland. Spot Ben Nevis trying to hide behind a cloud ;-)

I can ride our tandem Charlotte with John for about an hour (10 miles or so) before fatigue sets in and nerves fail to get the message through to my muscles. It's a gradual thing, in practice John contributes more and more power and I less. The well-worn tandem insult 'she's not pedaling at the back' is in part true ;-) A welcome rest for photos here (near Port Appin)

Getting off is interesting, John has become adept at leaning round, grabbing my left leg and lifting it over the rear allowing me to disentangle from the tandem and collapse to the ground to recover. Tandem Club friends, family and even complete strangers have stepped in to assist with this many times. If insufficient recovery time available the reverse exercise must be performed to get me back in the saddle again. Recovery time is best spent in cafés :-) or in the Highlands, ferries were a welcome rest too ;-)

My pal Justin in France is the same age as me, has similar MS and yet cycles solo. He's an ace cyclist and regularly does long hilly rides in the Pyrenees. His neuro in France cannot understand how is still able to cycle so well and once commented that if he were unable to cycle he would probably be using a wheelchair to get around! Justin loved the irony of this, as his love of mountain-biking in his younger pre-MS days had on numerous occasions almost put him in a wheelchair. Despite his amazing cycling ability, Justin often relies on fellow cyclists to lift him safely down from his bike to rest before he is able to stand. If cycling alone he has apparantly perfected a technique of falling off into a suitable bush!

This was Justin and me during Justin's fundraising ride from North Wales to the Pyrenees in August 2016. We are demonstrating our n=2 study showing that MS is not linked to genes controlling height.