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.
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.
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.
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!