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Deep brain stimulation treats high blood pressure (standing on giants’ shoulders)

The treatment involves inserting a thin wire electrode into the brain and connecting it to a battery-powered pacemaker

As an academic functional neurosurgeon implanting deep brain stimulators mainly for Parkinson’s disease and sometimes for tremor and dystonia, I was delighted to see recently published a case report of deep brain stimulation to treat high blood pressure.  The surgery was led by Mr. Nik Patel, a consultant neurosurgeon in Bristol and a friend whom I last saw over some huge plates of seafood and game in Cape Town half a decade ago.  He placed an electrode in the midbrain periaqueductal grey (PAG) matter in a woman with a blood pressure of 300/170 mmHg who had tried eight types of medicine, chronic baroreflex activation therapy and renal nerve ablation.  Her blood pressure initially became much lower at 170/110 a week after surgery, creeping up to 230/140 two years later, suggesting some long-term tolerance to the therapy.

The scientific paper was unusual in transcribing an interview between its author and an editor, and in that Nik was quick to acknowledge the basic science and human studies done in Oxford by Mr. Alex Green under Prof Tipu Aziz’ and Prof David Paterson’s supervision over a decade ago, and more recently my research under Alex Green’s supervision.  We were disappointed therefore to see newspapers such as The Express and The Daily Mail give no mention to over a decade’s research of ours that underpinned their first in man study.  While superficial journalism from the tabloids is not unusual, their articles mirror Bristol Hospital’s  and Bristol University’s press releases, neither of which make any mention of Oxford.

Self-promoting revisionist narratives are not uncommon either in science or in politics.  To repeat a quote from Indira Gandhi that my sister enjoyed,

There are two kinds of people, those who do the work and those who take the credit. Try to be in the first group; there is less competition there.

I have previously commented that modern biomedical science often progresses in small, incremental advances rather than Eureka moments and the Bristol institutions’ failure to acknowledge Oxford gives me an ideal opportunity to set the record straight and outline the incremental discoveries at Oxford that led to Nik’s elegant clinical study.  These were also coincidentally the subject of my Hunterian Professorial Lecture to the Society of British Neurosurgeons in 2014.  They can be summarised as follows.

In 2005 and 2006, we published that stimulation of the PAG during surgery in awake humans receiving DBS for chronic pain can elevate blood pressure if done dorsally and lower it if done ventrally.  Magnitude of blood pressure change correlated with magnitude of pain relief.  An important finding also published in 2006, this made the cover of the journal Pain.  These findings in 16 patients were the subject of Alex Green’s doctoral thesis with Tipu Aziz and won them numerous prizes from the American Congress of Neurological Surgeons, the Royal Society of Medicine and Neuromodulation amongst others.

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In 2010 I published a case of sustained reduction in blood pressure over 24 hours concomitant with pain relief with ventral PAG DBS on versus off, using ambulatory blood pressure monitoring.  That same year we published a detailed study using heart rate variability (an established measure of sympathetic tone) to characterise differences between ventral PAG’s more parasympathetic and dorsal PAG’s more sympathetic mechanisms of action in blood pressure control.

In 2011 Nik’s group published a case of reduction in blood pressure without pain relief in PAG DBS performed for chronic pain.  At the time I suggested in the news that

What their case report shows is that blood pressure can be reduced in a sustained fashion in a patient with unsuccessful deep brain stimulation for pain

In 2013 we published a large case series of DBS for pain suggesting that it is effective long-term in select aetiologies.  In 2014 I thoroughly reviewed the field of deep brain stimulation for chronic pain.  The patients receiving PAG DBS whose blood pressures had been studied were included in this cohort.

In 2013 we reported that the reduction in hypertension seen at one year in our patient receiving successful DBS for pain was not sustained at five years with presumed neurodegeneration.  This finding predicts the tolerance phenomenon seen in the current Bristol patient at two years after surgery.

Mr. Green continues to publish sophisticated research investigating the role of the human PAG in blood pressure control and sympathetic tone.  In 2016 we published a book together on the subject!

Bristol has precedent in performing first in man case reports of DBS building on decades of Oxford science.  Prof. Steve Gill’s pedunculopontine nucleus DBS for freezing and falling in Parkinson’s disease came about thanks to several years of rigorous animal research from Prof. Tipu Aziz, Prof. John Stein with their then doctoral student, and my now London Clinic consultant neurosurgeon colleague Mr. Dipankar Nandi.  The neurosurgeons in both cities have always been quick to acknowledge each other. Prof. Gill’s fellow, Mr. Puneet Plaha, who studied the patient even finished his training with me at Oxford and is now a successful brain tumour expert there.

Scientific progress is often fuelled by competition, conflict and rivalries and Sir Isaac Newton put it best.

Pigmaei gigantum humeris impositi plusquam ipsi gigantes vident

If I have seen further it is by standing on the shoulders of giants

It is rumoured that Newton meant this as a thinly veiled insult to his great rival Robert Hooke who was a man of diminutive stature.  Having studied at his alma mater and experienced first-hand the dry humour of its Fellows, I can well believe this.  Functional neurosurgery however exemplifies his observation in its romantic rather than its sarcastic form, so much so that a decade ago I began my published comprehensive history of stereotactic and functional neurosurgery in the UK ‘from Horsley to Hariz’ with his quote.  The Bristol and Oxford surgeons all acknowledge each other’s important contributions.  Their media officers perhaps lack such tradition and respect.  But then they probably don’t stand on giants’ shoulders.

In the mean time, please contact Mr Alex Green in Oxford or Mr Nik Patel in Bristol if you have a systolic blood pressure of over 300 and want deep brain stimulation.  While I am interested in related research into PAG DBS for the autonomic dysregulation of spinal cord injury, I am not brave enough to insert electrodes deep into the brains of patients with blood pressures that high!

St George’s deep brain stimulation service half a year on

Almost half a year on from starting the UK’s first new deep brain stimulation (DBS) neurosurgical service in half a decade, I am humbled by how our team has pulled together and flattered by the positive and gracious responses we have received from our first ten NHS patients so soon after the initial surgeries.

Two examples include:

I found Mr Pereira to be very open and honest as he explained the long process of DBS surgery to myself and my wife. He took his time, was relaxed and responded to all questions. He is extremely easy to talk to and his confident approach is very reassuring. We both felt inspired by him and knew I was in good hands. He came to see me immediately after the surgery in the recovery area. He calmly gave us an update of how the operation had gone and ensured we knew how to contact him and others if there were any issues during recovery and post-operatively. We’d like to thank him and the entire team involved in my surgery and stay at St George’s, it was an excellent experience.

and

Mr Pereira took on board all my concerns and acted on them although it made the surgery more complicated for him. He carried out the surgery without shaving any but the smallest patch of my very long hair and placed the battery at the top of my breast where it is invisible except with the lowest of necklines. Psychologically it helped so much. After fine tuning the stimulator I am feeling much better and can’t thank him and the St George’s team enough.

I can’t help but smile at the hyperbole of another patient:

Mr Pereira is quite simply the best of the best. Although his own brain must be the size of a small country and he has a talent given to very few people in the world, his ego is tiny and his compassion and humanity are great. DBS is not everyone’s idea of fun but he took time to explain it in the weeks before the operation in layman’s language, he was open and honest about the risks, and on the day itself he had an air of quiet authority which was immensely reassuring .And he was kind.

In my view, Mr. Pereira is a credit to neurosurgery, to the whole medical profession and to mankind.

There have been and continue to be challenges, difficulties and areas for improvement.  Nonetheless, achievements of the service to be proud of include that we have evolved slick and comfortable awake assessment during surgery and accurate electrode placement with no need for revisions and no infections so far in our early cohort.  We are implanting and programming deep brain stimulators from the three major manufacturers: Boston Scientific, Medtronic and Abbott / St Jude Medical.  We have appointed a superbly qualified service coordinator and expanded our clinical nurse specialist commitment.  Our expert academic neurologists have begun to gain support and salaries for their NHS commitments (which I hope will continue!) and we are starting to develop novel and exciting research projects around Parkinson’s disease, other movement disorders and neuromodulation in general.

All of this is a great excuse for our hard working team to share a celebratory cake!

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Fixing the head to the spine (and the broken bones in between)

The head sits on seven bones of the neck, perfectly balanced like a ball on a stick.  Three of these cervical vertebrae are quite different from the others in shape and in function – the seventh on which the others perch and the first and second upon which the head sits.

Whole books have been written about the ‘craniocervical junction’ and some neurosurgical authorities make their names and reputations in it.  I enjoy craniocervical surgery and often think it and intradural surgeries are two of the operations that fall more into the repertoires of complex spinal neurosurgeons (versus complex spinal orthopaedic surgeons).

The atlas (C1) rotates on the peg of the axis (C2) and the head flexes and extends on the atlas, all of these structures being attached by several short, strong ligaments and muscles.  In a variety of conditions from trauma, infection, cancer, abnormal development to rheumatoid arthritis (much more rare in the last decade with modern advances in disease modifying drugs), these bones or their attachments can become broken or deranged, necessitating fixation.

The neck can be ‘fixed’ simply by wearing a hard collar for a couple of months, but it does not always fix in the right position and the bones may not always unite in the correct orientation.  An alternative is fitting of a halo jacket which uses four pins in the skull and a tight fitting mould over the shoulders and chest to keep the neck rigid.  It can be uncomfortable, difficult to bathe in and, for some, difficult to breathe easily in.  I have seen the best results from halos in children, rather than the elderly who more commonly fracture cervical vertebrae.

There are several operations that can fix C1 to C2, should their connections be disrupted by breaking part of the odontoid peg of C2 or the ring of C1 for example.  In some circumstances a  ‘peg screw’ placed through the front of the neck can pull it down and into alignment and fix it in place.  More commonly, the fracture is such that surgery from the back of the neck is indicated.

We recently published a significant case series of a very strong construct for fixing C1 to C2:

Combined C1-C2 Transarticular with C1 Lateral Mass Screw Fixation for the Treatment of Atlantoaxial Instability: A Single Center Experience

I contributed most of the patient data to this case series, operated on by one of my complex spinal surgery mentors, Mr. Tom Cadoux-Hudson.  I was proud to publish the results in an Indian journal, firstly because the operation was first described by an Indian neurosurgeon who has made his name in the craniocervical junction, Prof. Atul Goel of Mumbai whom I once met in Kuala Lumpur in 2010 and who was most cordial in encouraging me to visit and see how he operated.  Secondly because around that time, I published a case report on the same operation to treat a particular type of infection by the spine grandly called La Maladie de Grisel, and had a slightly heated correspondence with him about the origins and nuances of his ‘double insurance’ operation.  Finally, the paper was a career defining one for my contemporary at Oxford University Hospitals, Mr. Murtuza Sikander, who also trained in India and was recently able to establish himself at Oxford after its publication.

There are a few methods of fixing C1 and C2 posteriorly:

The early Goel method which we describe in the paper.

Magerl’s method of just passing a long screw through the joint between C1 and C2.

Harms’ method of passing C1 lateral mass and C2 pars screws and joining them with rods on each side.  This is most surgeons’ (including my) preferred method as it is very strong with less risk of vertebral artery injury than the above two methods.

Slightly more historically,

Brooks’ fusion

Gallie fusion

All of this illustrates that there are many ways to skin a cat, even (especially?) in neurosurgery and complex spinal surgery and that one should choose an experienced surgeon exposed to most if not all of these methods and comfortable with at least one which they choose for good clinical and scientific reasons, not just because that’s the one they were taught.  With more experience, I now perform a different operation (Harms) to the one I was first taught (early Goel) as I think to all practical purposes it is just as strong, but less risky and less difficult to do well.  Neurosurgeons shouldn’t do the most difficult operation they can just because they think they can.  It comes back to the Hippocratic aphorism that entitles the recent bestseller of my St George’s consultant neurosurgeon colleague whose many stories from the neurosurgical frontline I thoroughly enjoy listening to, Mr. Henry Marsh.  Do no harm.

Writing books and learning neurosurgery by questions and answers

I recently published a book mainly aimed at doctors doing neurosurgery for their post-graduate end-of-training examinations, both the US residency boards and the UK FRCS(Neuro.Surg) exams among others.  It was quite an undertaking largely tackled by its hard working first author.

Neurosurgery Self-Assessment: Questions and Answers

It’s only my second foray into academic book publishing.  My first book published earlier in 2016 was more of an academic monograph related to my doctoral research with Mr. Alex Green and Mr. Jonathan Hyam in

Surgery of the Autonomic Nervous System

I have written over 20 book chapters, notably chapters on epilepsy surgery and imaging in the well known neurosurgical textbook Schmidek and Sweet, and recently the Basal Ganglia chapter with Prof. Tipu Aziz of the famous medical tome Gray’s Anatomy.  However, to write a whole academic book is a much more daunting commitment over a couple of years and it’s very gratifying to learn that the final product has been well received both in print and in its interactive online versions on ExpertConsult and Inkling.  The book is unique in containing the type of extended matching questions increasingly used in the British and other examinations.

I am delighted to learn from Elsevier that the question book is a best-seller among the neurosurgical community and that they are now doing a reprint within a few months of its release.  This gives us a great opportunity to incorporate feedback from the trainees and established neurosurgeons who have read it and spotted any first edition typos or other minor points for correction!

Amount of spinal tumour removed determines how much leg function improves (and experience, not tick boxes, turns novice neurosurgeons into experts)

Much of surgery consists of intuitive decision making.  This, in part, explains why patients seek out experienced surgeons.  It is hoped that neurosurgical experience, be it personal, from reading or researching, or from observing others, creates a rich frame of reference to draw upon when making both clinical decisions and fine hand movements  when manipulating someone’s brain or spine during an operation – or reacting to the unexpected.

I have an interest in surgical education and there is a particular scientific literature on the amount of experience and cognitive processing of it required to transition from novice to expert which is quite intriguing.  It’s often oversimplified to 10,000 hours  – which is probably the clinical experience gained in a good British neurosurgical training programme, although no high quality studies have been done either to confirm this or the validity of the many tick box exercises that UK neurosurgical trainees now have to go through.

I recently published a paper looking at clinical outcomes of surgery for spinal ependymoma, a particular type of common spinal tumour occurring intradurally (inside the dura mater lining the spinal cord and spinal nerves) and arising from ependymal cells that line the internal fluid spaces of the spinal cord.

Optimising treatment strategies in spinal ependymoma based on 20 years of experience at a single centre.

As a study of 61 patients with spinal ependymoma, it is one of the largest single centre studies published.  We confirmed what many surgeons suspect intuitively – the more tumour that is removed, the better the patient’s outcome, both in terms of survival and improvement in leg power and function.

On deeper analysis, the finding is not quite as intuitive as it sounds because the tumour surgeon’s dilemma is whether removing the last remnants of a tumour might damage normal functional neural tissue and cause a new deficit.  This is a particular challenge in eloquent brain tumour surgery and numerous tools from special dyes and awake surgery to intra-operative stimulation, electrical monitoring and transcranial magnetic stimulation have been introduced to assist resections.

The message is that careful and diligent gross, total resection of intradural spinal tumours remains desirable for best outcomes.  This is something that I endeavour to do in my practice as a neurosurgeon and complex spinal surgeon.  Transient, and unfortunately permanent, weakness remain risks of surgery on spinal tumours, but in my experience aggressive surgical resection confers best outcome.