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.

pain cover.jpg

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!

Advertisements

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!

IMG_2096.JPG

Can deep brain stimulation or spinal cord stimulation improve spinal cord injury?

This is an exciting field of research.  I am lucky to be working as an academic consultant neurosurgeon in a University Hospital with an academic neurosurgeon colleague, Professor Marios Papadopoulos, an experienced general, complex spinal and vascular neurosurgeon whose current research is yielding fascinating insights into acute spinal cord injury (SCI) that may change its initial treatment and improve outcomes.

One of my research interests lies at the interface of spinal cord injury and neuromodulation with the question of whether brain computer interfaces can improve the disabling signs and symptoms of SCI.  We just published a review of the field:

Surgical Neurostimulation for Spinal Cord Injury.

SCI is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress in scientific understanding, regenerative therapies are lacking. In this review, we outline the current state and future potential of invasive and non-invasive neuromodulation strategies including deep brain stimulation, spinal cord stimulation, motor cortex stimulation, transcutaneous direct current stimulation and repetitive transcranial magnetic stimulation in the context of SCI. We consider the ability of these therapies to address pain, altered sensation, weakness, blood pressure and bladder problems (autonomic dysregulation) associated with SCI. In addition to the potential to make important contributions to SCI treatment, neuromodulation has the added ability to contribute to our understanding of spinal cord neurobiology and the pathophysiology of SCI.

The prospect of using spinal cord stimulation to improve spinal cord injury is appealing as it is a procedure I already perform regularly to treat chronic pain when medicines don’t work.  Similarly, I do deep brain stimulation surgery frequently to treat Parkinson’s disease.  I also perform deep brain stimulation and motor cortex stimulation for chronic pain, but unfortunately these treatments are generally not NHS funded so I can only do the surgeries privately or internationally.

My own doctoral research during my neurosurgical training investigated the role of deep brain stimulation of a structure called the midbrain periaqueductal grey to relieve chronic pain, and its effect upon autonomic function, supervised by two established academic functional neurosurgeons at Oxford University, Mr. Alex Green and Prof. Tipu Aziz.  Modern biomedical science progresses through incremental discoveries building on a body of knowledge and expertise, rather than Eureka moments, so to investigate deep brain stimulation for SCI would be a natural continuation of that award winning research.

The first deep brain stimulation surgery at St George’s Hospital, London.

I performed the first ever deep brain stimulation surgery at St George’s Hospital for Parkinson’s disease in September 2016.  This was the culmination of three months of intensive effort from our dedicated team of neurologists, nurse specialists, managers and operating theatre staff.first DBS.jpgThe happy patient (pictured with permission together with our team – Lucia Ricciardi, Francesca Morgante, Alison Leake and Dominic Paviour) posted a touching testimonial on iwantgreatcare as follows:

I have Parkinson’s disease and for many years have sought to have deep brain stimulation (“DBS”) as a way of managing the effects of this illness. I was fortunate to be selected by the Movement Disorders Team (“MDT”) at St George’s Hospital at an assessment meeting during which I met Mr Pereira for the first time. During the meeting we discussed various aspects of the procedure and I immediately felt a bond with Mr Pereira due to his calm, forthright, assured and confident manner. Everything that I read about him confirmed him to be eminently qualified to perform this operation and so I had no hesitation in proceeding. The operation was performed on the 20th September 2016 at the Atkinson Morley Wing of St George’s Hospital. Before, during and after the operation Mr Pereira took time to make himself available to me for questions and re-assurance. During the operation, which is fairly invasive and during which I was kept awake, Mr Pereira kept a dialogue going with me to put my mind at rest and to keep me appraised of what they were doing and what stage they had reached. The operation has been a complete success and I look forward to many years of an improved lifestyle due to Mr Pereira’s skills as a surgeon and as a personable and approachable person. The wounds created by the operation have fully healed and were very neatly performed. I recommend Mr Pereira most highly as a skilled and caring neurosurgeon.

Thank you!

Deep brain stimulation is a brain operation where electrodes are inserted deep into the brain with great accuracy, in this case to structures of the basal ganglia to improve signs, symptoms and medication doses in Parkinson’s disease.  The electrodes are connected to a ‘brain pacemaker’.  Thousands of people have received the treatment worldwide.  I learnt the nuances of this operation in a craft apprenticeship with Professor Tipu Aziz in Oxford over the last decade.

medtronic-image