CPC: Chronic Deep Brain Stimulation and Hypertension

CPC: Chronic Deep Brain Stimulation and Hypertension

November 6, 2019 0 By Bertrand Dibbert


– My name is Anna Dominiczak
and in behalf of my co-chair who is not Professor Rhian Touyz but Professor Garry
Jennings from Australia who kindly stepped in, Rhian had to leave. We welcome you to this session which is a special session funded by American Heart Association on behalf of the Journal Hypertension and this is a clinical,
pathological conference. We film this session and
there are special rules here of engagement for both the
presenters and the audience. So, you will see the two
cases, puzzling, difficult, very, very interesting will be presented and there will be time
for really engagement with the audience and a big discussion and we would like colleagues
who come to microphones to not only identify themselves but also afterwards to
come and give their names with correct spelling
and the email to Denise. Denise is in beautiful
red jacket in the front. Denise wave to everybody and Denise will make sure that
your comments are captured and if appropriate and if you so wish, you’ll become a co-author of the paper that will be both as film on our website and as a paper in our
journal so great opportunity. Just talk a little and have
a paper in hypertension, doesn’t happen everyday
so you’re very encouraged to participate please. So, without any further ado, our first case will be presented by Dr. Erin O’Callaghan and Dr. Patel both come from Bristol, United Kingdom and they will talk about
chronic deep brain stimulation decreases blood pressure in
sympathetic nerve activity in a drug and a device
resistant hypertensive patient. Please come up here. – [Erin] Okay. – [Anna] Will you have enough space? – Yes, I think we will have
Nik sitting where you are so he could easily access. Great. Okay, good morning. First, we’d like to thank
the hypertension editors for inviting us here to present this really fascinating case. So, the structure of this talk, I’ll first, because it’s
a bit of an unorthodox treatment for resistant hypertension. I’ll first go into a bit of the background of the technology with the rationale for its use in the hypertension and break for questions before going into the actual case. Also disclosure, deep
brain stimulation devices are not currently labeled
for use in hypertension. So, as the audience is well aware, up to 40% of
patients with hypertension remain unresponsive to treatments despite the plethora of
antihypertensive medications that are available and approximately up to 14% of these patients
will be resistant to medications and this is really driven
a need for new strategies to treat high blood pressure. And in response to this we
have seen quite an advancement in the range of device-based
treatments for hypertension and the most widely used at the moment, well-established at the moment
are renal nerve ablation and baroreflex activation therapy which Dr. Jens Jordan discussed
in his talk on Wednesday. Now, you noticed both of
these device-based therapies aim to address autonomic
imbalance in hypertension and specifically aim to decrease
sympathetic nerve activity. But despite their availability, there is still a large number of patients that are not responsive to drug or device-based therapies and
this is why we’re introducing deep brain stimulation for consideration. We came across this technique
through Dr. Nik Patel who’s beside us here. He’s a consultant neurosurgeon at North Bristol NHS Trust Hospital and he routinely uses this technique in treatment of patients
with neuropathic pain or Parkinson’s disease and he published a case
report not too long ago which presented a patient that he’d prescribed deep
brain stimulation or DBS for the treatment of
intractable neuropathic pain and this patient also happened
to have high blood pressure an ABPM of 158/87 despite quadruple antihypertensive therapy. When deep brain stimulation was implanted and initiated in this patient, he observed a significant decrease in systolic blood pressure
that was maintained such that all antihypertensive
medications could be removed and it was maintained below
120/80 for three years after initiation of DBS. Now, this might not be remarkable if it went for the fact that
the patient’s, oops, sorry, patient’s pain levels
returned to a pre-DBS level within only a couple of months. So, this was the first observation where a change in blood pressure was dissociated from a change in pain and that led us to consider
that deep brain stimulation could be useful for central
target of hypertension. So, a part of the mechanism of this, the location that Dr.
Patel uses in this patient for the electrical stimulation is the ventrolateral periaqueductal gray and we know from a lot of
human and animal studies that this part of the brain is a region that coordinates the defense response and it receives neuronal inputs
from higher brain centers and coordinates an output
via brain stem structures and these outputs have direct projections to control sympathetic nerves
driving the vasculature. And there’s also recent
evidence that manipulation of this brain target can
improve baroreflex sensitivity which could be another
way which we can control, to provide long-term
control of blood pressure. So, what we have is an
intuitive brain target that we can use clinical technique
of deep brain stimulation to manipulate arterial
pressure in patients. So, deep brain stimulation whilst it’s new to the field of cardiology, it’s quite well-established
in the field of neurology and has been in use for over 20 years. It was first described for use
in treatment of chronic pain but is more commonly now
treated for the movement especially Parkinson’s disease
for which it has FDA approval and also the UK equivalent which is the National Institute for Health and Care Excellence approval. It’s also being tried for multiple other psychiatric disorders from epilepsy to addiction and depression. In Bristol, at North Bristol NHS Hospital, DBS has been in use since 1997 and they’ve implanted
well over 800 patients to date successfully. It has an excellent safety record that’s less than 0.3% reporting
of serious adverse events particularly of hemorrhagic stroke and the majority of
these were asymptomatic. And part of the safety or
the reason for the high level of safety at our hospital
in this technique is the technology and methods that is used for implant of the electrode. So, there’s quite a lot of effort that goes into the
pre-planning before surgery for the implant of the electrode. Once the select brain region is, once the target brain region is selected, CT angiography and MRI are used to plot optimal trajectory
of the electrode where you can specifically
avoid blood vessel damage and avoid other brain nuclei
to reach the brain target and this also has an
incredible level of accuracy where we can reach brain targets such as the ventrolateral
periaqueductal gray which has an area of approximately
three millimeters cubed and region can be targeted with less than 0.5 millimeters of error so we have highly precise and direct way of implanting electrodes. In the patients to receive the electrode, we use a robot-assisted stereotax so with laser-directed
optimization of the targets. under general anesthesia, the patient can be implanted, first with the guide
cannula along the trajectory and a dummy electrode can be placed in this guide cannula such that on table CT
can be used to confirm that the electrode is
in the correct place. The dummy electrode can now be removed and replaced with the active electrode which is implanted, secured, and then, the lead is
tunneled subcutaneously to the implantable pulse generator that can sit in the sub-clavicular pocket. Now, importantly, after
the patient has recovered from this operation, the physician can then externally control
the outputs of this device and the multiple contacts on the lead that sits within the
brain and the physician can activate individually
the different contacts and the outputs from each contact such that you optimize the
area and volume of tissue that is activated by the stimulus. So, what I’ve shown you here
is a very precise technique for activation of a target brain region which we’ve been selected the ventrolateral
periaqueductal gray as a target for controlling blood pressure, and we’re happy to answer, oops, sorry, any questions and after questions, we’ll present the first time
we’ve used this technique to treat someone with drug and device-resistant hypertension. – [Anna] Okay, anything
to add, at this stage? – Just to reaffirm that this is a very well-established technique and is used in the treatment
of Parkinson’s disease and since its inception
over 100,000 patients have been treated and
that’s an exponential rise in the future. And so, in terms of the
technology and the invasiveness, it’s well appreciated. We’ve actually developed
a very, very streamlined robot-based method of application
under general anesthesia without any distress and under
very serene circumstances and hence, the hurdles
towards adopting this providing we prove correctly that it maybe effective would be less so. – Okay, could we have
questions from the floor? Could you please come to the microphone and identify yourself. That’s absolutely essential
because we’re filming. (participant speaks off mic) – Whether this is done once or how frequent would that be necessary? The stimulation or is it a permanent? I was a bit late, perhaps I missed this part of the presentation. How frequent? Is this something you do once or how sustained is this procedure? – In terms of implanting the procedure, or implanting the electrode, it’s just done once and it’s connected to a implantable pulse
generator or pacemaker which is situated underneath the clavicle. – And how frequently do you need to do the actual stimulation or is
it a continuous stimulation? – It’s a continuous
stimulation at low frequency and we’ll show you some of the parameters as the talk evolves and
it’s a rechargeable system and because it’s on very low frequency, the patient has to recharge the generator usually once every three
weeks for about an hour. – Okay so, the second microphone first. – Sean Stocker, University of Pittsburgh. You just commented a
little bit on my question but I was wondering if as the
presentation moves forward if you can comment upon how
the stimulation parameters are established, you mention
that the periaqueductal gray is about three millimeter cube distance and so, when you start to
think about current intensities and indirect side effects
as far as affecting other brain regions, I was curious. As the presentation moves
forward if you could comment upon how those parameters where established. – Go. – You know well, we can,
I’ll start by illuding to where I implant the electrode, it’s usually to the depth
of the superior colliculus to minimize spreading
to the oculomotor nuclei and and in terms of the frequency, we know that low frequency
has stimulatory effect and in terms of treating pain, or, the analgesia effect is based on low frequency as well. Now, the early work done in
animal models and in humans in the acute setting
within the operating room was done in Oxford and
they found that stimulating at low frequency in the ventral part of the periaqueductal gray
resulted in a hypotensive effect and on the converse
stimulating the dorsal part of the periaqueductal gray resulted in increase in blood pressure. So, we had some basic science and acute studies in humans that directed us as to what
we would need in these cases when we implanted it. – With most forms of chronic physiological nerve stimulation, you
get some sort of adaptation. And is there any suggestion
in the other applications of this technique if that happens? – Yeah, as was established in this case, the gentleman actually had a
good acute response with pain, however, this does not
last beyond three months and that tolerance,
luckily was not extended to his blood pressure control. We also found that if we
switched the system off, and often it’s used into
counteracting the tolerance, we were no able to
reestablish the pain response but we could reversibly
alter his blood pressure. So, when the system is switched off, his blood pressure would rise
and when it was switched on, we can reproducibly bring it
back to a controlled level. – Okay so, we have a second
microphone again and then– – I’m Salgado from University
of Sao Paulo, Brazil. Maybe I have missed the information, how many patients have you
implanted and did the stimulation and did you combine the MSNA recording in order to show that there
was a sympathetic inhibition? – So, the patient we
referred to just before, there was no muscle sympathetic
nerve recording in that. That was a novel serendipitous finding. The patient that we’re going
to present in this second half, we have done MSNA recordings. So, I will show you that data and to date, the patient that we’re
presenting in the second half, that is the first patient in the world to receive DBS solely for hypertension. – [Helio] Thank you. – We could get onto the case. So, we have one more
question. – Maybe they just answered my question but what are the plans for
randomized trial or control, control study?
– Obviously, based on the evidence we’ve already seen, it’s yeah, on the way. (laughs) – Okay.
– We will present that and show our suggestions. – With ambulatory blood pressure? – Yeah.
– Yes, the whole shebang. – Let’s see how convincing the case– – The case, yeah.
– Then we’ll discuss that. – Fairly confident you’ll be convinced that her blood pressure is
exceptionally high and resistant. Okay so, as promised, let’s move on to our really interesting case. So, this lady, she first
developed hypertension at the age of 37 and this followed four successful pregnancies without evidence of preeclampsia. She’s a German lady, she’s 51 years old when she first presented
to us and postmenopausal. She’s not obese, quite the opposite, she’s incredibly slim and her BMI is 18. She is non-smoker, not diabetic, and she does have focal epilepsy and this was diagnosed after her development of hypertension. And there’s some familial
history of hypertension. Both parents are hypertensive and her father had an MI at 70 years old. Both are still alive. So, as I said, she’s first
diagnosed at the age of 37 by her German GP and her
pressure at that time was 160/90. It progressively increased
despite drug treatment according to the current guidelines and she was classified
as resistant hypertensive by the age of 41. And by the age of 43, despite
the drug interventions, her blood pressure had
reached more than 220/120, and this acceleration in her
increase in blood pressure is quite fast and is a bit atypical of essential hypertension
as we understand it. So, she was sent to a hypertension clinic, was referred to a hypertension clinic for investigation for secondary causes. However, they found no secondary causes which I’ll go over in the next slide and her blood pressure not only was it not lowered by further treatment but it continued to rise and reached 280/130 millimeters
of mercury by the age of 46 which led to her further referral to a specialist hypertension
clinic in Hannover which is a center for tertiary
referrals for hypertension where she underwent further
investigation and treatment. So, she was quite comprehensively screened for secondary causes and these were published not that long ago in a case report in Hypertension
by Schroeder et al., and they described the
techniques that they used for excluding the secondary
causes listed here. They also confirmed that she was compliant with her drug regime by
drug metabolite analysis as well as observed oral
ingestion of her medication and her drug medication managed to reduce her blood pressure, this was measured by intra-arterial line from 280 to 250 millimeters of mercury. So, it didn’t, it wasn’t
addressing her severe hypertension. So, as I said, during her visits to the hypertension clinics in Germany, they optimized and titrated
her medication list but by the age of 46, she was taking eight
antihypertensive medications daily and I’ll go over those, what
they were in a little bit. As this obviously wasn’t
controlling here blood pressure, she was referred to the
hypertension clinic in Hannover, and they investigated her
for autonomic dysregulation and potential eligibility for what was the new clinical trial at that time which is baroreflex activation therapy. So, she was enrolled in
this trial and received the First-generation Rheos CVRx Barostim and initially, it was successful in treating her blood pressure and reduced her systolic pressure by 60 to 80 millimeters of mercury. However, after three months,
it continued to rise again and exceeded its, well,
reached its previous levels. So, two years later, she was enrolled to receive renal nerve ablation and she underwent Symplicity catheter, RDN Symplicity catheter,
renal nerve denervation by a highly experienced
clinician in this technique. However, this had absolutely no
effect on her blood pressure. And at this stage, she became, she was quite desperate for new treatments and she actually discovered Dr. Patel’s previous case report from
her own internet searches and contacted him directly,
nearly begging for enrollment in a trial to receive
deep brain stimulation. So, we couldn’t resist having her arrive. A patient this exceptional. So, we invited her to
Bristol to undergo screening and she was screened by a cardiologist, Dr. Angus Nightingale in
his hypertension clinic at University Hospital Bristol. And we attempted to use a standard automated blood
pressure cuff on either arm, we were unable to get a
reading from this lady because the cuff could
not reach the limits. Her blood pressure exceeded the limits that were detected by a cuff and for anyone that’s not aware, the cuff limits are 299
millimeters of mercury. So, we confirmed with a manual
aneroid sphygomanometer, we went old school and
this showed the dial was fluctuating wildly between 300 and 350 millimeter systolic. So, that confirms that her
pressures were absurdly high. We connected her to a finger
pletysmography, Finapres for about an hour while she was lying down on a bed relaxed and her
pressures were maintained above 300 millimeters of
mercury for this period. We where curious how much
this high blood pressure was a white coat effect so
we attempted a 24-hour ABPM, probably optimistic so
we, and, not surprisingly, we only had one successful
reading at 235/140, the rest of the readings
being unsuccessful due to her pressure being too high to be detected by the ABPM. And these high pressures
are confirmed or corroborate her previous home, she
keeps quite a strong record of her home blood pressures and visits her GP fairly regularly. And she was reporting that
when she could measure her blood pressure, it was
in the region of 280 to 290 and her GP confirmed this and this was in the two
years prior to seeing us. And in the one year prior to seeing us, more often than not, she was unable to record
her blood pressure. And just to remind you
that these pressures are extremely high in the face of baroreflex activation
therapy, renal nerve ablation, and eight antihypertensive medications. And these medications are listed here and you’ll notice that there
are eight different drugs and these drugs cover
seven different classes used for antihypertensive treatment. The doses of which add up
to a whole drug equivalent of nearly 13 and for
those that aren’t aware, most resistant hypertensive patients will be on the equivalent
of less than four whole drug equivalents. So, she’s received quite
an army of medications to try and control her blood pressure which have been unsuccessful and this is obviously
quite a list of medications to be taking daily which is not ideal. So, to her symptoms, she does suffer from symptoms of her high blood pressure. She gets severe headaches about
one to three times a month and these are debilitating headaches that leave her bedridden. She feels generally unwell
and severely lethargic. She was unable to work
due to feeling of lethargy and was often in bed by five o’clock because she was too exhausted to continue. In terms of her other signs,
she has only mild concentric left ventricular hypertrophy and mild hypertensive retinopathy. She doesn’t have any evidence
of other end organ damage. No microalbuminuria,
she hasn’t had a stroke or a ischemic heart disease or infarct. So, she’s quite impressive
in that she’s maintaining these extremely high blood pressures without enormous side
effects and end organ damage. So, before we considered implanting her with a deep brain stimulation device, we wanted to make sure that
our hypothesized method of action would be useful for her. And as we expect the
deep brain stimulation is reducing sympathetic nerve activity, we wanted to make sure that she actually had high sympathetic nerve
activity to begin with given that she’s had all these therapies that are supposed to be reducing it. So, Dr. Hart used microneurography to measure her muscle
sympathetic nerve activity and she found that she
had at rest 56 bursts per 100 heart beats. And when normalized for body weight ’cause she had quite a low body weight, this did show that she
was much higher than women at a comparable age that are normotensive. So, we thought this justified
use of deep brain stimulation to try and help her
lower her blood pressure. So, this is now showing you
the results and data from DBS. This is before receiving
deep brain stimulation and these recordings are
arterial pressure and heart rate from her home blood pressure diary which she keeps rigorously. And these are on eight
antihypertensive medications daily and with baroreflex activation therapy. So, you can see the she was averaging between 260 and 300
millimeters of mercury systolic for the two years prior to DBS. So, we implanted DBS and switched it on and in the three months
following initiation of DBS, her blood pressure had
decreased dramatically. And she was feeling a little tired from, just feeling at bit tired so her antihypertensive
medications were withdrawn to prevent her blood
pressure from dropping lower ’cause despite them still being above what the recommended target was, this was obviously having
side effects for her. So, in the year follow up afterwards, her blood pressure did rise a little bit in the year following DBS. However, her heart rate was also rising which meant that she was reinstated with a beta-blocker, Metoprolol, and this was the only
medication that was reinstated and she refused any further
addition of drug therapy. So, we don’t know if this pressure could still be brought down further again by adding more drugs to her daily list. And this is, we’ve followed
her out for two years now and her blood pressure has stabilized at this new lower baseline about 220/140 millimeters of mercury. And whilst this is still
considered quite high, the patient reports to
be feeling much better. She doesn’t have as, well her headaches occur less frequently and are less severe. She’s back to work and she works on a farm and she’s also back to horse-riding. So, she’s enjoying her
quality of life a lot more at this new lower pressure. So, she kindly allowed us to
continue investigating her from a mechanistic perspective
and allowed us to measure her muscle sympathetic nerve activity after DBS was initiated
and on the left here, if you can’t see clearly the scale, this is Finapres blood pressure
270 to 140 scale before DBS and you see a larger number of
bursts, MSNA bursts occurring compared to three months
after deep brain stimulation, there were fewer bursts and this new scale is 230/130 I think. So, her blood pressure is
lower and her MSNA is lower three months after DBS. We, again, recorded her
MSNA a year afterwards and this is the graph I showed earlier with her before DBS
levels of normalized MSNA. And she’s now sitting comfortably within the normal range of MSNA but normal is strange word to use given how high her blood pressure is she’d had no MSNA whatsoever. So, based on this, we
think we have treated her blood pressure by
reducing sympathetic activity using this technique. So, to summarize before questions, what we’ve shown here is
the very first use of DBS to treat solely for the use
of treating hypertension. We’ve shown that it was
safe in this patient and effective at decreasing
her blood pressure and we think this does
justify systematic testing of this technique in patients
with very high blood pressure that are resistant to current
drug and device therapies. In terms of this patient
in particular, her future, we very like to hear
what your thoughts are given that her blood pressure
is still over 220/130 and she doesn’t have that
much end organ damage given this longevity
of her high pressures. We are wondering if perhaps
she needs high pressure to perfuse these target organs and we’re considering if perhaps she has some vessel
tortuosity that’s causing, that’s driving up her pressure to be able to perfuse
the organs adequately. But as I said, we’d very
much like to hear your input and before we break for questions, I’d like to acknowledge the team of people that have helped with this patient. With Dr. Patel, his team at North Bristol NHS Trust Hospital, the team at University Hospitals Bristol and CRIC Human Research Lab as well as the University
of Bristol, Dr. Paton and our collaborators at
Hannover Medical School here. So, thank you and we look
forward to your questions. (audience applauding) – I think, this is really
an extraordinary case. I suspect that in the
audience, not many people have ever seen blood
pressures of this number. Could we ask the audience
by raising the hands up. Have you ever seen
systolic blood pressures and diastolic of that level
sustained over period of time? I calculated that this is 14 years and so little end organ
damage, it’s incredible. Could we have a show of hands? Anybody ever seen pressures like that? Right, I haven’t, so very few so I hope– – Does it count if it’s the same person? – It doesn’t, sorry,
at the back there, doesn’t count. The same patient doesn’t count. – The true test is, is when the mercury flows up the top of the sphygmomanometer. – So, I’m not persuaded by the argument that she needs this pressure
to perfuse her organs. In that case, we would
have seen many patients of that type and we do not. There is something really unusual. So, I think, Professor
Luft is going to say this but can I, before he comes, can I ask, you haven’t shown us any pictures, detailed brain architectures,
MRI’s et cetera. They must have been done. Was there anything abnormal in this brain to drive this blood pressure? – She had had MRI scan
before she came to us and it looked entirely normal with also very little,
small vessel disease change and subsequently, I used
that preexisting MRI because I could not do another MRI scan in view of her implanted Rheos system. – Yeah. – And I used a CT scan which
aligned perfectly with that MRI so there was no change in cytoarchitecture or small vessel disease phenomena or anything to suggest
multiple end organ TIA and related changes. – Okay, we’ve got a question. – I’m Lars Lindholm, Sweden. I’m fascinated, of course, by your story here about patient. Could you tell us a little more
about this lady? Apparently, she’s a
skinny lady with four kids going about life just as any ordinary. Is there anything else in the, I mean, you must know a lot about her. I mean, how can she cope with
this, this blood pressure? – [Erin] That is exactly what
we’d like to know as well. – I mean, isn’t there anything, it’s just headaches, of course, but intermittent headaches
but nothing else? – I mean, she had a history
of presumed epilepsy, we’re wondering whether
this was syncopal– – Yeah.
– Phenomena. But without TIA-related event but she was incapacitated regularly and every month, she would have periods where she could not function and usually because of
these intractable headaches. She was on medication for angina as well but didn’t suffer significant
bouts of chest pain but we were equally bemused and my first response when I saw her email was probably to run in
the opposite direction. – [Lars} Well, I suppose
you need to invite her to one of our big meetings. We can all meet her and see her. – She’s a remarkable lady
and would be very pleased. – So, I think we have first
microphone and then Fred Luft. – So, George Roush from UConn What is the correlation between the level of
sympathetic nerve activity, and the expected blood pressure? Is it higher than, are there data correlating these two variables? – Well, it’s difficult
in premenopausal women that’s not so correlated,
but in postmenopausal women such as our patient and in men, there is a correlation between
high sympathetic activity and higher blood pressures but we don’t have a huge understanding yet of the causative role in the, well, I think actually, the other day, there was quite a good figure showing that the progression of higher
sympathetic nerve activity in patients that are normotensive,
borderline hypertensive and resistant hypertensive
and it does increase with the increasing
pressures in those patients. – [George] Yeah, sure but I
assume that the blood pressure is much higher than one would’ve expected for that level or nerve activity. – Yes, yes, it is, absolutely. – But just on that, we do see people with other disorders who are normotensive such as panic disorder,
some people heart failure who’ve got these kind of burst frequency so it’s not a direct relationship. – Okay, Fred Luft. – Fred Luft from Berlin. This lady was under our care when she was in the Berlin area for several years and then when Jens Jordan and Christoph Schroder moved to Hannover, they took over her care there. There are several remarkable things at these kinds of pressures, her sympathetic nerve
activity ought to be zero. – [Anna] Yeah, yes. – And that’s not zero at all. She had MR angiography as I recall looking at this puditive
neurovascular contact syndrome at the rostroventral medulla and that did not appear to be the case. She reminds me of the genetic hypertension that we’re studying
that’s caused by mutations in phosphodiesterase 3A
because these people also have normal sympathetic nerve activity at profound blood pressures and they also have no target organ damage. They die of stroke,
presumably, cerebral hemorrhage although we don’t know that for certain because we didn’t have an
opportunity to study that since they respond to medications but it takes three classes but they do respond to medications. One comment and a question, I think it might be worth, and
I’m sure she would allow this. We never gathered cells from her if she would undergo at fat biopsy, we could culture mesenchymal stem cells and convert these to vascular,
smooth muscle cells and look to see if the
pathways are somewhat similar to what we found in this
genetic form of hypertension. My question is, would
bilateral stimulation be perhaps more effective
because it looks like you’re about halfway there? – It’s a good question. We do know that with
unilateral stimulation of the periaqueductal gray,
you will get bilateral effects and the stimulation will
spread across the midline. I think the risk of putting
two electrodes maybe outweigh trying to capture more
changes in blood pressure. I still feel we have maneuver
and room for reprogramming to try and enhance the effect
that she has sustained to date and throughout she’s being fairly adamant that she does not want any
further antihypertensive therapy reintroduced and felt
that the side effects from this were intolerable. – Okay, I think we have that last question at the microphone, yes, yourself. – Irv Zucker from the
University of Nebraska. One way you can get increases
in sympathetic nerve activity in the face of high blood pressure is by enhanced input
from excitatory inputs from the periphery. We have a study that we’re
showing this afternoon in SHR Rats showing that ablation of dorsal root ganglia
afferents in the thoracic region can reduce blood pressure and you mentioned that
she suffered from angina. I wonder if there were
any other pain syndromes that could be driving the
increase in blood pressure even if there’s not a
conscious awareness of pain and the second comment is whether or not the deep brain stimulation
is activating vagal pathways such as would occur for vagal stimulation for depression or Parkinsonism, Do you have any insight because since you did microneurography, you probably did things
like cold pressor tests and Valsalva maneuvers to
evaluate those two arms of the regulatory pathways
for sympathoexcitation? – We didn’t do those regulatory tests, we didn’t feel comfortable with
it given her high pressures – [Irv] Yeah, right. – But they were conducted previously by Jens Jordan and his team I believe. And she was found to have normal baroreflex control impressively. – [Irv] Really? – Yeah, what else was I going to say, oh. We do know also from, with regards to this deep brain
stimulation and vagal control. We do know from a lot of animal work that there are direct projections from the ventrolateral periaqueductal gray to cardiac preganglionic neurons. So, we assume that they could potentially some effects there we haven’t analyzed it specifically in this patient. – Would Dr. Jordan like to comment? You’re very welcome. No? No, no comments? Okay, right. Are there any other final
comments from the floor? I think this is an incredible case and we’re really, really
keen to publish it with all your comments because I think that will be something that
will stay in the literature and will be referred to for years to come as a case of extreme hypertension. It’s more than resistant, it’s sort of super resistant hypertension. So, any last comments from the presenters? No, you’re happy with the way
we discussed, my co-chair? – I’ve just got one last
question for the audience. How many of you are ready for
a randomized control trial– – Good question.
– Put your hand up if you think and how many would like a bit more information before– – Nobody wants to do, oh yes, there’s one, there is one, two.
– Yeah. – Okay.
– Okay, we’re not very brave
clearly, not very brave. – I’m not sure we can leave it at this but let’s move on to the next case anyway. – Okay, so thank you
very much, presenters. (audience applauding)