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INSIDE HEALTH – Programme 6.

TX: 24.10.17 2100–2130

PRESENTER: MARK PORTER

PRODUCER: ERIKA WRIGHT

Porter

Coming up today: Brain surgery for epilepsy – normally regarded as a last resort, should it be considered earlier? I meet a neurosurgeon who thinks surgery is underused particularly in young children.

Clip

So this is you, Lucy, when you had electrodes put in your brain, do you remember? And we had those little spikes in your head?

Yeah.

So this is the bit I was talking about, you see there’s your dragon, there’s his head, there’s his upper jaw, there’s his body, there’s one wing and there’s his tail there, you see? And the bit of you that was causing the seizures was that bit under there, the bit under – the rock under his chin right there. Lucy’s dragon.

Porter

And a novel use for statins – could they help fight off infections like pneumonia? Adding another string to the drug’s bow that might burnish their somewhat tarnished image.

Clip

Statins are like the Marmite of the medical world. Some physicians and researchers love them and some absolutely hate them. And there is a massive drive to include them in research on one side and a massive drive to limit prescription on the other. So it’s really important to work out what the true science is behind them.

Porter

But before that, a more conventional approach to treating pneumonia.

Antibiotic ad

Part of the ad that forms the mainstay of the government’s latest campaign to cut antibiotic prescribing in a bid to reduce the growing threat from multi-resistant bacteria.

Antibiotic ad

GP Dr Margaret McCartney is in our Glasgow studio. Margaret this is an ongoing campaign, is the tide turning?

McCartney

It’s a good question. And I’m not sure that it is. We know that the number of antibiotics prescribed overall has reduced between 2012 and 2016. But the problem is it’s not an even distribution. So GPs, for example, have decreased their use of antibiotics by 13% over this period; dentists by 20% but in secondary care – hospitals – there has been no sustained drop, although some antibiotics have declined in use slightly but there’s certainly been no drop in antibiotic use overall by them.

Porter

Do we actually have evidence that prescribing fewer antibiotics has an impact on resistance or is it too little too late possibly?

McCartney

We certainly do know, there is evidence that says that if you are prescribed an antibiotic in primary care for a chest or a urinary infection you’re more likely to develop bacterial resistance to the antibiotic you were given for usually the first month afterwards but can persist for up to 12 months afterwards. So for an individual there does seem to be an effect. In terms of what the community effect is I simply think we do not know, we don’t have enough high quality data to tell us.

Porter

Do we have any evidence of harm through trying to cut back inappropriate prescribing in that we’re slower to prescribe antibiotics in chest infections, for instance, does that mean that some people might be slipping through the net and being seriously ill with pneumonia?

McCartney

It’s a really good question because some gross figures, looking at hospital admissions for different things, would suggest not. But what’s I think quite interesting, looking at the data, is there has been a big increase in antibiotic prescriptions by out-of-hours and urgent care centres, which overall they hardly prescribe any antibiotics compared with general practice as a whole but that is a bit of increase and I do wonder whether that means that perhaps people are going to out-of-hours services when they’re not getting them in-hours. So it’s difficult to make a judgement about that. We do know that there has been an increase in a condition called gram negative sepsis, that doesn’t seem to have decreased, which had been the hope with antibiotic switches in the community to try and target in particular urinary infections more effectively with different antibiotics. So it’s hard to know without looking carefully at case notes and having contemporist discussions to know exactly what the magnitude of harm in cutting down prescribing is. But I certainly think there’s a lot of benefit to be had from cutting it back.

Porter

The campaign’s aimed at both us, as prescribers, and our patients, as people who are taking the antibiotics. Looking at patients – I mean people – GPs – often talk about they feel with some patients under pressure to prescribe, even though it might be inappropriate.

McCartney

Yeah there’s absolutely no doubt about that. When you go and do qualitative research asking doctors why they’ve prescribed antibiotics a lot of it comes down to I think a fear, a lot of the time, about doing the wrong thing in not prescribing. Now we know, there’s good data that tells us, that antibiotics have lots of problems attached to them. But the problem is if a patient wants something and the doctor wants to please them almost it can feel far easier to do the easier thing rather than to do the right thing. There’s lots of other information about this as well. So, for example, there was a study published a couple of years ago saying that doctors with lower prescriptions of antibiotics in their practice tended to have lower scores on the feedback tests – the friends and family tests that patients are sent out – they were less popular as practices. There’s also data from North America saying that the later in the day it is the more likely doctors are to prescribe antibiotics inappropriately in what they call decision fatigue. So there may be lots of other things going on in the consultation that doctors are doing which is not actually related to the patient in front of them but the circumstances and environment in which they’re working.

Porter

Margaret, are you noticing from a personal perspective there’s any change in attitudes, either amongst your colleagues or the patients that you’re seeing?

McCartney

I certainly think I am seeing more people now who are keen to say at the beginning I really don’t want to have antibiotics unless I really need them, which I of course highly respect. And I suppose a lot of the time antibiotics do only ever offer marginal benefit, for sore throats and many chest infections and it is rational to avoid using them when we can.

Porter

A lot of the coverage suggests that patients want antibiotics. And in my experience most patients do not want antibiotics but there’s a hard-core of people who still believe that they’ll cure everything.

McCartney

Yeah, unfortunately and I think that this has been propagated by doctors, to be honest with you, over many years. Sometimes you look back into ancient notes and you just see sore throat – amoxicillin – and that’s the only note that there is. So I think that doctors have been our own worst enemies, we almost taught people to expect antibiotics for things when they never were going to work in the first place.

Porter

And we must shoulder our fair share of that responsibility. Thank you very much Margaret.

Well, one all too common, and deadly, infection crying out for alternatives to existing antibiotics is pneumonia. Around a quarter of a million people are diagnosed with the lung infection every year in the UK – around 30,000 of whom will die – nearly all of them elderly.

Pneumonia can be a serious threat at any age but if you’re older, you’re much more vulnerable.

Respiratory Consultant Dr Elizabeth Sapey is checking up on a recent admission to the wards at Queen Elizabeth Hospital Birmingham.

Actuality

Sapey

How are you feeling today?

Patient

Well not too good, the breathing – my breathing has been bad.

Sapey

Your breathing’s bad, I’m sorry to hear that. Do you mind if I have a listen to your chest? Oh dear you’re coughing.

Porter

Antibiotics are the mainstay of therapy in pneumonia but there haven’t been any new drugs since the 80s.

Actuality

Sapey

Let me have a listen in and see what it sounds like. Just take some steady breaths in and out for me. That’s lovely, keep going. Well you’re quite rattily in there still. I think there’s quite a bit of phlegm to come up.

Patient

Yeah it is quite – I bring quite a bit up.

Sapey

Well good.

Patient

Okay thank you very much.

Sapey

Alright, see you tomorrow.

Porter

Mr Gibbons’ doctor, Liz Sapey, is also Managing Director of the National Institute for Health Research Wellcome Facility, and on a quest to find new ways to improve pneumonia therapy. And she may just have succeeded with a very surprising drug, which is why I’ve come to Birmingham to meet her.

Liz’s work focuses on the immune system and why advancing age makes us more susceptible to pneumonia.

Sapey

What happens is your immune system is much less effective at recognising an infection but once it gets there it doesn’t switch itself off. So you have this low grade inflammation present that doesn’t end as it should do. And that makes it less efficient at dealing with infections but also more damaging to your body and to the tissues in the body.

Porter

So to use an analogy – the troops are late to the fight and then after the battle’s won they’re hanging around in the town drinking in the bars – is one way of looking at it.

Sapey

That’s exactly right yes.

Porter

And what’s changing in the immune system to cause that shift in behaviour?

Sapey

If you’re thinking about infection one of the most important parts of the immune system that deals with infection is a cell called the neutrophil. They are your most abundant white cell in the body. They circulate around in the bloodstream, only living for about two weeks, but when there’s infection they go from the bloodstream to wherever that infection is, so your lungs if we’re talking about pneumonia, and then they mop up that infection and then get cleared by other cells of the immune system. And what we’ve found is as people get older the ability of their neutrophils to track infection to arrive there accurately and efficiently and then clear the infection have been reduced. And we think that’s one of the major components as to why older people are so susceptible to pneumonia.

Porter

When you’re talking older people?

Sapey

Well I’m afraid I’m coming into the bracket where my immune system isn’t going to be working so well. It’s when you get to your 50s, which is a bit of a shock. And essentially your immune system is a little bit inefficient from when you’re young, which is why children get more infections till about 16, 17, then it works very well until you get to your 50s and then I’m afraid it starts to tail off a little bit. And it tends to go hand-in-hand with frailty – so people that are less able to do their activities of daily living, less able to walk as effectively as they could before and it tends to go hand-in-hand with those chronic conditions that so many of our population suffer with – diabetes, heart disease, stroke. So the more frail you are the more burden of disease you have, the more likely it is that your immune system won’t work very efficiently.

Porter

This explains perhaps why people who are older are more susceptible to pneumonia but how does it help us as clinicians looking after somebody who’s ill?

Sapey

Well if you know that their immune system isn’t going to work as effectively you can try treating with antibiotics but we know that’s only half of the answer in our patients with pneumonia. As a clinician what you would like to do is give somebody something that would switch on their immune system and be able to make it act more efficiently and at the moment we don’t really have any tools for that and that’s what we’ve been working on.

Porter

Liz and her team have focussed in on a pathway within the immune cells that affects the behaviour of neutrophils and it’s the same pathway that cholesterol lowering statins act on.

Add that discovery to research, by Liz and scientists in other centres, that suggests people taking statins tend to fare better when they develop pneumonia and a tantalising theory emerges. Could statins be used to bolster the immune response in older people?

The team in Birmingham has demonstrated that adding Simvastatin to the neutrophils in the lab enhanced the white cells’ ability to target bacteria and, crucially, stand down when the job was done. Statins were making the neutrophils more efficient.

The next step was to test the effect in people.

Sapey

So we started with a healthy older group of people, so they were all over the age of 65 and they were otherwise pretty healthy. But when we looked at their neutrophil function we could see that it was reduced compared to younger people. And we gave them either Simvastatin or a placebo for two weeks and we looked to see what happened to their neutrophil function. And what we saw is that their neutrophils were much better at getting to the site of infection and clearing bacteria. So what we’d seen in the lab actually happened in a person and that doesn’t happen very often in science.

Porter

So the next logical stage is to do a randomised control trial in real people with real chest infections?

Sapey

Absolutely. Well it hasn’t been published yet but I can tell you that we saw an improvement in neutrophil function, we saw a reduced death rate and reduced re-admissions to hospital.

Porter

I mean that’s amazing.

Sapey

I know.

Porter

I mean it’s a small study.

Sapey

It’s a small study. Now what we have to do is a multi-centre trial in many more patients with pneumonia.

Porter

And unlike most novel therapies, statins have been around for years and are off-patent meaning they’re cheap. Simvastatin costs just a few pence per tablet.

Sapey

We know that the development of new antibiotics will lead to antibiotics being available to will cost a lot of money and some of those antibiotics just aren’t available to a lot of places in the world. But you could treat someone with Simvastatin for literally – what a pound for a five day course? It’s something that would be accessible across communities.

Porter

Is there any evidence of statins having a useful immune boosting response in any other types of infection that you’ve come across?

Sapey

Yes, so there are some studies looking at things like urinary tract infections, which show a similar response, it’s the same cell doing the same thing, just going to your bladder rather than to your lungs. But really interestingly if you think about statins helping the immune system target more effectively and then turn off the damaging effect we also are starting to see benefit in statins in things like some forms of dementia, for diabetes as well, which we think are chronic inflammatory diseases as well, which we also believe the immune system has a massive role in, in terms of how these conditions develop. So statins probably have a lot of utility across a number of inflammatory conditions and infections.

Porter

The pathway that statins work on has lots of potential effects. I mean if it’s working on the immune system in one way is there the potential that it might be working on the immune system in a bad way as well, that we’ve not yet identified?

Sapey

I think that is something to consider. We’ve looked at different cells of the immune system but we haven’t covered all of them, as you can imagine, and the cells that we’ve looked at have either shown a positive effect or no effect. But that’s the whole point about doing a clinical trial in lots of different people because sometimes it throws up something which you weren’t expecting and that’s why I certainly wouldn’t recommend at the moment doctors out there prescribe statins when a patient comes in with an infection, that would be the wrong thing to do, the evidence is promising but it’s not conclusive.

Porter

What were the patients’ responses and the responses of their families when we said we’d like to add in a statin?

Sapey

It was mixed, as you can imagine, but actually the majority of patients and the majority of families were really excited and keen to be involved.

Porter

I’m intrigued as to what sort of response you might get from the medical community, you say your paper’s not published yet, because there’s a pretty vocal anti-statin action in medicine and in the general public as well.

Sapey

Absolutely, they’re the Marmite tablet aren’t they, I mean some physicians and researchers love them and some absolutely hate them and there is a massive drive to include them in research on one side and a massive drive to limit prescription on the other. So it’s really important to work out what the true science is behind them.

Porter

I get the impression talking to you – and I expect the listeners will too – that you’re very excited by this?

Sapey

Oh goodness me, so there have been no outcomes that improve pneumonia since 1984 – 1984! And that was when Co-amoxiclav or augmentin, an antibiotic, came to the fore. So this is the first thing that we’ve seen that has the potential to improve outcomes in pneumonia, so of course I’m excited.

Porter

Liz Sapey. And you will find more information on pneumonia on the Inside Health page of the Radio 4 website.

Brain surgery for epilepsy may sound a bit drastic, particularly as the condition is normally controlled by pills, but there is a growing belief among neurosurgeons that surgery is not just a treatment of last resort, but that it should be considered more often, and at a younger age.

Two years ago, Mark Nettle and his wife had a call from school about their eight-year-old daughter, Lucy, she’d collapsed in the playground.

Nettle

She was rushed off to hospital but she – was it on disco night? – yeah and fairly quickly after that there was a diagnosis of epilepsy. We then spent a year sort of trying different drug regimes – anti-epilepsy drugs – but a very frustrating year really because whichever combination of drugs were tried she was still having the seizures. For anybody who’s not close to somebody in the family with epilepsy you don’t realise the devastating impact it has, particularly in a child, all the things that you can’t do, they’re fraught with danger or you find yourself not doing them – whether it’s swimming or a climbing frame or a sleepover with friends. And actually at the end of that year, so in the summer of 2016, we had the absolute nightmare scenario of being on a Spanish campsite in a Catalan speaking area of Spain, neither of us being able to speak any Catalan, and Lucy went into a – I think it’s called status…

Porter

Continual seizure.

Nettle

Continual – and ended up in A&E in Gerona in Spain and a great battle with our insurers to get her flown home. And…

Lucy

You had to bring me sausages.

Nettle

…I did fly you sausages all the way from Somerset didn’t I, that was – yes they were very nice in customs.

Porter

The seizures were getting worse and anticonvulsant medication wasn’t controlling them. Lucy was transferred to one of UK leading paediatric neurosurgical centres at Bristol Children’s Hospital. The section of her brain triggering the seizures was identified using an array of implanted electrodes and then, three weeks ago, Lucy underwent complex surgery to remove the offending part. An anxious time for all involved.

Nettle

I think because of the devastating impact, both on Lucy and on the family, of having frequent seizures I suppose we felt we’ve got nothing to lose here and everything to gain. That doesn’t mean that you then relax over an afternoon waiting for your daughter to emerge from the operating theatre – I think our nails were chewed down to the bone – but felt for quality of life we had everything to gain really.

Porter

Lucy’s operation was performed by Consultant Paediatric Neurosurgeon Mike Carter.

Carter

Epilepsy very much is a childhood problem, a very high proportion of cases will actually start off in the childhood years. I would say that 90% plus of the adult cases I see started off having seizures before they were five years of age.

Porter

Most people listening will be very familiar with the medical management, the use of so-called anticonvulsant drugs, anti-epileptic drugs. Where does surgery – where has it fitted in historically?

Carter

Well I think surgery has always in some part been considered as a potential remedy for difficult to control seizures. Even in these days of modern anticonvulsant medications we know that roughly one-third of patients who actually have seizures will not respond to medications of any sort and it can often take many years to get to that point of understanding that you don’t have a response. And of course during that period seizures can wreak terrible damage on a developing brain – socially, academically and all the things that you’re required to do in order to maintain a normal adult lifestyle. So I think that increasingly we’re now beginning to perceive surgery as something that you do earlier in the batting order of things that you might want to use for treating seizures than one of the last possible things. And that’s a perceptual thing really that I think the enlightened need to start telling to those who suffer from seizures, will actually often know this themselves and of course also to their carers because there’s still quite a resistance to the idea of using epilepsy surgery for even really cases that are likely to respond, even amongst the physicians that look after these patients.

Porter

You’re a neurosurgeon so you would say that.

Carter

Well I am a neurosurgeon but I’m also a physician, I’m also a parent and I’m a parent who has other friends who are parents of children, some of whom have epilepsy. So I’ve seen at close hand really what a terribly devastating – this disease can be. I think that the cementing of the role of epilepsy surgery in treating epilepsy in this country has partially come about more recently because of a joint investigative attempt by the International League Against Epilepsy, which is a big epilepsy charity in this country, and also the Society of British Neurological Surgeons, who back in 2011 launched a position paper that pointed out that not only was epilepsy surgery incredibly effective in treating some kinds of epilepsy, it was also massively under-utilised. And really that’s why we have these four nationally designated centres in the United Kingdom designed specifically to coalesce resources and expertise in the management of complex epilepsy in children.

Porter

Has our understanding of what’s going wrong in the brain of someone with epilepsy changed in recent years, is that what’s driving this?

Carter

It’s partially that, I mean I think that the brain after all is an electrical organ and its function depends upon ordered patterns of electrical activity being propagated across its surface. So it doesn’t take very much for something relatively minor to disturb that and cause what we see as an epileptic fit. In many respects it’s like an electrical storm raging across the surface of the brain. We know now that there are individual areas of the brain that can malfunction and cause seizures, we know that there are all kinds of things that can contribute to that, for example, a genetic background or possibly a head injury or a tumour or some kind of developmental abnormality in the brain. Conventionally surgery has always looked to maybe isolate that area and remove it but you know with increasingly powerful mathematical modelling that we’re using now to analyse epilepsy we’re increasingly finding that there are fairly predictable pathways through which abnormal electrical activity can be propagated to cause the spread of seizure. So nowadays not only are we looking at removing or isolating the source we’re looking at potentially disabling some of the pathways of transmission. And that I think is a mathematical phenomenon as much as it is a surgical one and it’s a very exciting new departure for the potential treatment of hitherto untreatable epilepsy.

Porter

Lucy has come in for a check-up with her dad, Mark. She still has a bandage on her head but, looking at her, you wouldn’t think she had undergone such major surgery just three weeks earlier.

Actuality

Carter

Welcome back to the clinic, it’s lovely to see you, how are you Lucy?

Lucy

I’m fine.

Carter

Million dollar question – any seizures?

Nettle

No seizures in those 20 days, I mean I think we’re aware that it’s early days but of course for us it’s a novelty going 20 days without any seizures.

Carter

And just remind me – how frequently was Lucy seizing before surgery?

Nettle

Well it had various patterns in the two years since first diagnosis but the worst point about seven at night and two or three in the day. So you can imagine the change in our quality of life really following the surgery.

Carter

And I remember that when we saw you before surgery, she was developing progressive weakness down the left-hand side as well, difficulty with walking, I remember she came in a chair the first time we saw her.

Nettle

Yes she did, yeah, yeah.

Carter

And of course the difficulty of this operation was that the area that was causing the seizures, the fits, was right in the middle of eloquent cortex, which means bits of brain that do something, in this case bits that generate power down the opposite side of the body. How about you Lucy, what about you, you look incredibly well, do you feel okay?

Lucy

Yeah.

Carter

Okay. Any headache at all?

Lucy

No.

Carter

Any itching in your head where the scar was?

Lucy

No.

Carter

No. Are your arms and legs working properly? Can I stand you up for a minute? See what you can do, come over here a mo, you’ve got a splint on – you have haven’t you, okay. Can you stand on one leg? Can you – if I hold your hand – can you jump up and down on that leg? Not quite yet, so it’s still a little bit weak okay. How about on the other one…?

Porter

Mike Carter checks Lucy’s movements and then has a look at her scar.

Actuality

Carter

Excellent. Right, can I have a look at your head now? Can I take this off? Right, so we’ve still got the steri strips on, under there…

Lucy

It’s sort of peeled off.

Carter

Yeah it’s beginning to peel off up here as your hair grows. And the skin will be healing nicely now, it’s an S-shaped scar because if you retract an S-shaped scar it becomes a square box, that’s the basic geometry of it, okay. The actual bit of the brain we went to is in the part of the brain called the motor strip, which is just one side of the mid-line on the right-hand side and that area of brain was a thing called a dysplasia, a small area of mal-formed brain, sitting right in the middle of that motor area and that’s why we had to chase it down using the electrodes that were in previously and we were able to find exactly where the seizures were coming from and we were able to stimulate the areas around to find out that in fact that area wasn’t particularly functional and we resected it – removed a bit of brain from it.

Nettle

And is it apocryphal the idea that it was Lucy’s dragon – that it was a dragon shaped piece?

Carter

It really did look dragon shaped. Come over and have a look at this. So this is you, Lucy, when you had all your electrodes put in your brain, do you remember, and we had those little spikes in your head.

Lucy

Yeah.

Carter

So this is the bit I was talking about, you see there’s your dragon, there’s his head, there’s his upper jaw, there’s his body, there’s one wing and there’s his tail there, you see. And the bit of you that was causing the seizures was that bit under there, the bit under – the rock under his chin right there. Lucy’s dragon.

Porter

In terms of the size of the piece of brain that you removed, how big was it?

Carter

Very small, probably a thing about the size of your fingernail I would think, your little fingernail, imagine that in cubic dimension sort of thing, so it’s not enormous but you don’t need much malfunctioning brain to create a very serious electrical disorder.

Porter

So essentially you can overlay these on each other to come up with a plan?

Carter

And that’s exactly what we do. We have a wonderful capacity now called neuronavigation which means that we can coalesce maps of the brain both anatomically, physiologically and [indistinct word], which is what we need if we’re going to go into tiger country like the primary motor cortex. And of course the great thing about the young nervous system is its tremendous plasticity, so the overall drive to do bigger operations in younger people was very much designed to try and make the most of that plasticity because function can relocate in the brain if you do even quite destructive operations at an early enough age.

Porter

And by plasticity this is this concept that other bits of the brain will take over tasks that were done by the bit that you’re removing?

Carter

Exactly. Many functions of the brain are kind of like anatomically specific, so they tend to be located in one particular predictable area but that again is very variable and it’s certainly a function of age. So, for example, in some of the younger patients we see we’re able to remove or disconnect entire hemispheres of the brain and end up subsequently with a patient who’s effectively functionally normal. It wouldn’t seem possible really, logically, would it but in fact it is because it’s entirely possible for the brain to re-learn and to relocate those functions elsewhere.

Porter

And is that a time critical process? One would imagine as you get older that becomes less and less?

Carter

It’s very much a time critical process Mark, it doesn’t ever completely resolve, that’s how of course rehabilitation works after strokes and head injuries and what have you and we get great results from that in adults. But really before the age of about seven years the system is incredibly plastic and the closer you get to birth really the more plastic it becomes. And so we are now trying to treat epilepsy surgically at an earlier stage as is possible and that includes an increased national drive to operate on people who are suitable before their second birthday.

Porter

That’s very young.

Carter

That is, yes, but the results justify it.

Porter

Neurosurgeon Mike Carter and I am pleased to report that Lucy is doing well and hopefully back at school next week.

That’s it for this series of Inside Health but we are already working on the next series, so if there is something you think we should cover then please do get in touch – contact details are on the Inside Health page of the Radio 4 website. We will be back in the New Year, until then goodbye.

ENDS