Hi, and thank you very much for inviting me, I think this is my first time at this event.
So I do have lots of different hats, and so I did run the ENCEPH UK program grant, and I’ll give you a little bit of information from that but not too much.
What I was asked to talk about was “infectious encephalitis, causes and diagnosis” – which is a lot to
cover in 25 minutes, so I’m not covering it all. I’m gonna say “what is encephalitis?”
Now the vast majority of you will probably already know this but
there is a reason why I start off with that, and then we’ll talk a bit about
infections, because that’s obviously what I do day in day out as an infectious
diseases consultant, and then how we make the diagnosis and again I’m not going to
go into a lot of details because it’s, there’s a lot to cover.
So why do I say “what is in encephalitis?” and probably because there’s a big misperception in
the general public. You’re a different kind of public, okay? Because you know
more about it then the vast majority of people. They confuse what the difference
is between meningitis and encephalitis an awful lot of the time and, dare I say,
so do an awful lot of my colleagues, and there’s a lot of lack of understanding
even in the health care profession. Meningitis is the inflammation of the
lining of the brain: people have headaches, they have neck stiffness, the
lights bother them but cognitively their thinking is okay, they are not confused
their conscious level is usually not decreased. Whereas encephalitis is inflammation of the brain tissue itself and depending on which bit of the brain
is inflamed, then depicts what symptoms people will have.
So they may have very subtle changes in their personality and behaviour, which if a doctor doesn’t ask
other family members, may miss because they might look completely fine on that
initial consultation. Hence why families and relatives who are here – it is so
crucial that you come with relatives to hospitals to say “No they’re not right,
there’s something definitely wrong here.” And sometimes they have fits and
seizures, sometimes they have other obvious abnormalities
like weaknesses of a limb, and can be confused for being a stroke.
It’s difficult for clinicians, so do feel sorry for them, okay? Because there’s a
lot of overlap within encephalopathy: which is that there’s something else
wrong with the rest of the body, but they’re a bit knocked off, so they are
confused, so you can have a really serious infection and be a bit confused –
that doesn’t mean to say you’ve got inflammation of the brain tissue or encephalitis.
So there is a lot of overlap and it can be difficult at that
very first consultation to know the difference. What causes encephalitis?
I’ve broken this really simply, so antibodies on one side
infections on the other. I’ve only put up 1, 2, 3, 4, 5, 6, ok?
And there’s a whole pile of different bugs that can cause infectious encephalitis and I’ve not put the list.
If I give you the guidelines the list goes on and on and on.
But the big one in the middle HSV is the commonest cause.
So that’s why I’ve put it centre stage but there’s a whole pile of others
and I’ve put some in there on purpose. Measles and vaccination rates
going down, and we’re seeing more measles cases. Enterovirus is very common, rabies
I’ll talk about that a little bit later on, listeria.
But, and I’m going back this is an old slide, but it does show you HSV encephalitis is the biggest, commonest cause of
sporadic encephalitis – that’s why we talk about it first and foremost.
And then we’ve got lots of other little ones here as well. This is an old slide, and at that time a lot of them weren’t diagnosed. Then Public Health England (back then it was called Health Protection Agency) did a study in three
geographic areas: London was one of them, the southwest, and in Liverpool in the northwest. And they looked at the different causes of encephalitis and
no surprise HSV encephalitis was still the
commonest cause for the infectious ones, but this is when autoimmune antibodies
started to be developed or identified as being a bigger cause.
In this particular study there was a lot of TB overlap, there was also VZV (varicella zoster virus) and just pointing out on this slide, this study was adults and children. So there were other autoimmune mediated
types of encephalitis in this, like ADEM that happens more in children than in adults.
The study that you’ve just heard Phillippa talking about was this one,
there was a big program grant that I did and it looked at encephalitis in
adults and in children and the only reason I put it up is to show you that
HSV – this one here – is still the biggest cause of those infectious types of encephalitis.
So all of these are infections, this was a big mixed bag
most of this was VZV, the chickenpox virus, but there was lots of other ones
travel-related, there were immunocompromised patients in there with
some weird and wonderful viruses as well, you have some bacteria, and then this
chunk was the autoimmune. It looks like it’s more proportionally than the
previous study I showed you, but the definition’s changed. So it’s not actually
more when we break this down into specific antibodies. And we still have a chunk that we don’t ever find out what the cause is. Now sometimes I look at
these case records and I think, “oh well that sounds really much more like a
viral encephalitis we just never identified|” and others you think “no it
sounds more like an autoimmune type.” So you can get a feel from the story.
So talking about HSV, like I said it’s the commonest one, the vast majority of us in
this room have probably had HSV when we were children, and we’re very good when
we’re children, we share lots of things when we’re children we don’t have very
good hand hygiene so we share all our bugs with each other. And we’ll have
acquired it, and we won’t even have known it because there won’t have been any
infection at all at the time, and we will then, the virus will go up into the
the dorsal root ganglion which is a part in the spinal cord where the
nerves go, and it just goes there asleep and it stays there until every night
again it’ll wake up, come back down the the nerve and usually will come to the
lip and cause a cold sore. Every now and again it goes up the other way instead
of coming down it goes up and it goes up into the brain.
We don’t know why, for some people, if you’re unlucky that the virus starts to
multiply when going back up into the brain. And that’s where you get encephalitis. You get lots of inflammation, you’ve got lots of white cells that go into
where the blood vessels are, and you get some bleeding in and around here, so this
is hemorrhagic, and there’s cuffing around these blood vessels, and this
person obviously has passed away from their encephalitis, and there’s a
section of their brain, and you can see how much bleeding has occurred around
where all that inflammation has happened in this temporal lobe, so this is this part of the brain.
Patient journey – I love this slide – I put it together because
every person has a story, and every person’s journey is different and
understanding how people get to places is really important so you can be unwell,
but maybe talking with your friends and family, and you’re not quite right but
you don’t go and get any help, but other people will go straight away to get help.
The different symptoms that people have some will seek help quicker than others.
Where do they go for help? Well you might be just go to the pharmacy and get some
paracetamol because you’ve got a temperature, you might go to A&E, you might go to your GP, you might bounce back and forth between GP and back home again because they think it’s just a viral infection. Once you get into hospital
then there’s a number of investigations that should happen, but there’s
difficulties in recognising the symptoms that people have, and so there
might be delays here, and it’s easy to say “this is what should happen”, but it doesn’t always happen the way it should. And then there’s number of
investigations and we’ll talk about that. And there are different outcomes, and
people can bounce back and forth, their inflammation like an autoimmune might
come back and they have more and more problems. And I like this particular sub-study, this was one of my colleagues Jessie, who interviewed patients who’d had HSV encephalitis, so this is only the herpes simplex group, and they were very open-ended
narrative questionings about their experience. And she was not a clinician, so she just let people talk about how they were feeling before they came into
hospital, what their experience in hospital was like. And I’ve only taken two little snippets, and I’ve used lots of these snippets in different
scenarios for different reasons but for this one I’ve highlighted in green, just
some of the wording that people use and how you can see it’s vague and it’s
difficult to understand as a clinician actually what is going on. There’s lots of different things that this can be. “Unwell and a bit wobbly” – you know assess for a stroke, okay. Then they’re drowsy. “He’s not right” – this
is why I harp on about listening to family relatives. Strange symptoms,
tripping over, again this assumption that this could be a stroke. This gentleman
was in his 70s, this one was in his 30s. You can see how things can get clouded
when people look at an age of a person as well, and what’s the likelihood
of this being this particular condition or that particular condition instead.
So the story is really, really important and what Jessie did there was
very open-ended narrative stories – we don’t do that in clinical practice.
What we do as a doctor is take a very detailed history and it’s a story, it’s
just a different kind of story, but we’ll target a little bit more the
questions and the symptoms, and when did this start, and what the pattern and
evolution has been like. And the story will include also their past medical
history and I’ll demonstrate why that’s important, and their social history.
So if we think about symptoms, you might have a fever, you might not, you might have a
headache, you might not, you might be fatigued, you might not, you might be a
bit irritable… can you see where I’m going with this? Not everybody’s the same, okay?
The encephalitis will be different for different people, and it’s not always
barn-door obvious. It’s sad to say that if you are younger, and “knocked off”
cognitively, mentally, you come in you have a fit, someone will think of encephalitis probably far quicker than if you are older. And if you’re a bit
confused because they’ll say “oh well maybe they’ve just got an infection and
a little bit of dementia and it’s a bit worse.”
But if you’ve never met that person before you wouldn’t know that actually, normally
they’re crystal clear and they don’t have dementia. So there is this again, and
back to the relative being there to say “no, they’re not right, this isn’t what
they’re normally like.” One of the most recent diagnosis of encephalitis I
made was in a lady who had dementia but whose husband said to me “well yes
she’s got dementia, but she’s changed, she’s definitely different.” And by the
time I got to see her everyone else was treating her for a urinary tract
infection, and then I said “no, let’s do the lumbar puncture,” and she did encephalitis. So it’s all important even with someone who has got problems with
their brain function, like dementia, still not to assume that they can’t have encephalitis as well. The past medical history – so the story about what’s
happened before is really important, okay? And this is why infectious diseases doctors
take ages taking their histories because they go back a long, long time.
So if someone has had measles in the past that’s important to me, because measles
does have other sequelae that can happen later on in life. You can have encephalitis at the time of the measles, but you can also have one up to 20 years afterwards. So it’s important to tell me if you’ve had that. Likewise chickenpox there are different types of encephalitis you can get with chickenpox:
at the time of the rash, in fact I think it’s on my next slide, you can get one
that happens at the time of the chicken pox, or you can get one that
happens a week later, or many weeks later. And those patterns are different if
you’re younger or if you’re older. Again, for the measles if it happens quickly at the time you can have this primary measles encephalitis, but here you
can have one that can happen up to 6 to 15 years afterwards. Sadly if this one
happens people don’t survive. Travel history – so one of my bug bears is people
not taking travel histories. And we all go travelling for different reasons, we
don’t all go with our nice little suitcases and stay in lovely little
hotels, some people go backpacking and into the middle of nowhere and
having the adventures of their lifetime and don’t get any travel advice before
they go, and can pick up lots of different things when they’re out there. So I harp on to other doctors about
taking a good travel history. And these are just a couple of acronyms that we
use, but I’m really pernickety, can you tell? I want to know exactly where
you’ve been and exactly what you’ve been doing, and who you’ve been doing it with and that does mean all those details, okay?
We do ask all those details. If you’re visiting family and relatives, if
you’re going to a hotel, if you’re going to the beach, if you’re going to go to
safaris – I need to know all of that information, I need to know if you’ve
been vaccinated against various different infections or not or have
malaria prophylaxis and taken it, okay? We know when you haven’t taken it, and even you can get malaria though with breakthrough, even if you
have taken it, so you can be forgiven all right? Even if you’ve taken it religiously. But it’s really important for us to take that level of detail
because that’s what helps us to diagnose those infections when you come back .
So the story – where have you been? Well if you go to this part of the world
and you might have had some contact with some horses, you might have West Nile
virus encephalitis, you might have eastern equine encephalitis, there’s a
few nasty encephalitis viruses over there that you can pick up. If you go
over along this sort of route in the world, and if you go to Sweden, you go to
Austria, even go to the southern parts of Germany, the northeast of France, there’s tick-borne encephalitis if you’ve been uphill walking and things
like that, so I need to know about that. And there’s all the different risk
factors that you can get from picking that up. And if you go to any of this
part of the world, all depending on how long you’ve been in the country, what
you’ve been up, to whether or not you’ve been in rural areas, and you’ve been
anywhere near rice paddy fields, and these birds, and these pigs – this is where
Japanese encephalitis circulates in this life-cycle. Human beings generally
for all of these are dead end hosts, they don’t transmit onward infection, usually.
And I’ve just put up some nice, more lovely pictures – I do this to the other
doctors to try and scare them – but it’s important for us to think about
where the risks are because we often forget about risks. So, you can go to
Italy- bet you didn’t think Italy was very risky, did you? So you can go to Italy
and you can pick up sand fly bites and get Toscana virus, which can give you
a meningoencephalitis, and you can even get rabies in in Scotland –
that’s where I worked before I went to Liverpool, and that was
the first cases in the UK of a bat handler who got rabies Lyssavirus. That
was sad, because he was actually a bat handler it should have known better to
get vaccinated, and didn’t, so he passed away. There are a lot of people who go
travelling who don’t even think that they’re going to be at risk of rabies
and forget when they’re down by the beach and those lovely stray dogs that
come along “oh I’ll just pet this little dog” – nip – little bite, it doesn’t take much and can come back and won’t have anything for many many months, and there have
sadly been cases of patients coming back from their travels having had a dog bite
or a monkey bite and got rabies. I’ve got the ticks and hill walking in Austria,
there’s lots of tick-borne encephalitis there. Cats even in the UK can, if
they scratch you, usually kittens or stray cats, they can pass on an infection
called Bartonella that can cause an encephalitis. You can go kayaking around
the river’s edges, where the rats pee and there is Leptospirosis there, that can give you an encephalitis. Aedes, another type of mosquito, lots of different
viruses. Zika was in the news not that long ago, again can cause an encephalitis. And there’s lots of other viruses that these ones carry. Unpasteurised milk –
I do like my unpasteurised milk and I do like unpasteurised cheese, so I’m not
saying you can’t do any of these things but you do have to know that there’s
risks involved with them: Listeria, Brucella, they are in various cheeses in
various parts of the world. Have I put anybody off going travelling? The next
bit that’s really important to us in the history is when you’ve gone travelling,
and whether or not it’s at the height of meningitis season, going to the Hajj for
example. Is it at the end of a rainy season when all the mosquitoes have just
been multiplying, there’s lots of larvae everywhere, and then you’re more likely
to have dengue multiplying, things like that, and malaria as well. And then the incubation period, so I will add up it’s not good enough to tell me that
you’ve been on holiday 3 months ago I’ll need to know exact dates because
of the incubation periods for certain infections we’ll say “right, it’s not going to be that one because that incubation
period is only a week.” So arbovirus infections like Zika, like dengue, if
you’ve been back for more than a week that’s not going to be the cause and I
can rule them out straightaway. Things that take longer in their incubation periods,
Brucella will take a longer time, TB will take a longer time. So that’s why I harp
on about the dates. And then how long you’ve been in the country and that
exposure risk so if you’ve gone to Thailand and you’ve stayed in a city
hotel for a business meeting for 2 or 3 days and you come straight back
you’re not going to have Japanese encephalitis. But if you’ve been backpacking and you’ve been going around in rural areas for at least 2 months,
or a month, it doesn’t have to be specifically that length of time but a
long period of time, and you’re sort of exposed to those mosquitos you’re more
likely to be able to pick up Japanese encephalitis. So that’s why the
duration and exposure is important. Some of these are not wholly accurate because
time has changed, so for example rubella: it says mortality 0-50% that was one of the quoted papers that I
had. That’s because you have a huge variation when you have very little
cases actually happening. But mumps: mortality is not that high but look at
the morbidity, the long-term sequelae that people will have afterwards.
Likewise with measles, the mortality changes as to when you get it, but the
morbidity is very significant. Why am i harping on about those three? MMR.
MMR – people don’t get the vaccine for their children, and they’re putting their
children at risk of getting measles, mumps, and rubella. And we’ve had
outbreaks of measles, and we’ve had them in the UK, we’ve had them in Europe, we’ve
got them in the States at the moment and I’m just waiting sadly for the outbreak
of encephalitis to come with it, because I think it will come. That one
we can vaccinate, so please do. Others when you go travelling – get good
travel advice, because there are a number of these that there are vaccines for
that will prevent them, and if I could only show people what it looks like when
they’ve had these and the morbidity that they have afterwards
I’m sure everyone would pay for the vaccine afterwards. But sadly people weigh
up the risks and the benefits when they’re meeting a health care
professional and think “well I’ll be okay, what’s the chance of that happening to
me? It won’t happen.” And there are others where
there is no vaccine, so there’s still research that needs to be done there. In
terms of diagnosing, the main things that we do are: taking a lumbar puncture,
because we don’t do brain biopsies, or very rarely, but we try to find the
evidence of that inflammation somewhere else. So we get clues: if there’s
neutrophils, it’s more likely to be a bacterial infection, if there’s
lymphocytes, it’s more likely to be a viral infection. And then we look at them
either underneath the microscope and we’ll get them to culture them, or we
look at them in PCR methods – so different techniques of trying to find the
infections. Sometimes we take pictures of people’s brains and we might get clues.
Again none of this is barn-door because some HSV encephalitis might have
normal brain scans or they might have the classical signs in the temporal
lobes, here we’ve got Japanese encephalitis where it happens in this
part of the brain and the basal ganglia. Here you’ve got down at the back of the
brain this Rhomboencephalitis which happens at the base, and this is where
this inflammation is happening and this is Listeria for this particular one.
Here we’ve got a child that had CMV encephalitis and it happens around the
rims of the ventricles, which is why there’s lots of fluid in here. JC virus
has a different kind of picture altogether it has like a scalloped
appearance to it, and you can always have multiple bits. Here we’ve got VZV, again
inflammation of a particular organ right at the back the cerebellum that knocks
off the balance, which is why children when they get Cerebralitis, they can’t
walk straight and they walk very wide based. All of these are clues, okay?
There’s nothing that tells any of us as clinicians which particular infection it
is. The history will help point us in a particular direction, there’s a lot of
overlap with other conditions, and so we have to be methodological and go step by step to try and rule things out, go with what’s common and start investigating things.
HSV is the commonest type, we know that – so that’s why we jump in with the
acyclovir, but sometimes it won’t be that. But it’s important we get in treatment
really quickly, the longer you are in getting that treatment, the more likely
you’re going to do badly – so that’s why we harp on about giving acyclovir quickly. It’s very important as far as I’m concerned to take a good history
because the clues are always in the history, and especially finding out what
you get up to and where you’ve been, what jobs you do, what sports and recreation
you do, because there’s lots of infections that you can pick up there.
When we diagnose it we don’t do brain biopsies the vast
majority of the time, so we’re looking for clues in other areas, we’re looking
for those surrogate markers to tell us there’s inflammation there. And one way I
try to identify them: it’s blood tests, it’s CSF tests, looking for bugs in
different techniques. Sometimes we do biopsies, for TB we might do a biopsy of the lymph gland and find the bug somewhere else. EEGs: again these are the little
electrodes on the brain that look at inflammation of the brain. They’re not
specific, they won’t tell me exactly what bug it is, but they might give me a clue.
So it’s not as easy as maybe we’d like it to be, and it takes a lot of
detective work which is why I do the job that I do. For my study there was a lot
of people involved it wasn’t just me, it was a big, big study, and the
patients – you guys were crucial for helping with getting the information and
giving us the clues that hopefully we’ll help the next doctors
in terms of helping other patients to know how to diagnose patients with an encephalitis in the future. I hope that’s been helpful