Deep dive

Words: Viel Richardson
Portrait: Christopher L Proctor

What is deep brain stimulation (DBS)?
Mr Erlick Pereira: It involves using an artificially generated electrical signal to modify abnormal electrical activity in the brain. With DBS, we implant electrodes deep inside the brain and use a pulse generator to deliver electrical signals designed to control abnormal brain rhythms. The pulse generator is implanted in the patient’s chest, with leads running up through the neck to the head. These are connected to fine wires that are fed into the brain, at the end of which sit the electrodes we use to deliver the stimulation signals.

What is the mechanism by which the treatment works?
EP: When you want to move a part of the body, there is electrical circuitry deep in the brain that deals with the process of turning the thought about moving into the physical movement. In some conditions, this circuitry can transmit faulty signals or be constantly transmitting, giving the patient constant and potentially severe tremors. If you put an electrode in the right part of the brain, you can pass a high frequency electrical current in a waveform that effectively jams or modifies these abnormal signals.

What conditions has it been developed to treat?
Dr Dominic Paviour: The main one is Parkinson’s disease, which causes problems of tremor, rigidity and difficulty or slowness of movement. This is usually managed by medicines, but some patients’ symptoms can be improved significantly with DBS. Other movement disorders include tremor and dystonia, where sustained or repetitive muscle spasms can result in twisting or an abnormal fixed posture in the neck. Carefully selected patients with chronic pain syndromes may also respond to DBS.

What are the efficacy levels?
EP: We see some excellent results. For Parkinson’s, you will usually be able to halve the amount of medication the patient is taking while cutting the severity and durations of their symptoms by 50%. In dystonia, we see significant improvements in controlling spasms and relaxing the overactive muscles. It is also very effective in conditions involving tremors.

Does it work for everyone?
DP: Not everybody with these conditions is a good candidate for DBS and not everyone with these conditions would have symptoms severe enough to make the surgery worthwhile. For Parkinson’s disease, there are some very effective tablet-based treatments for controlling symptoms. For dystonia, initial treatment would be a combination of tablets and an injection of botulinum toxin into the overactive muscles. In the case of tremor syndromes, DBS is typically much more effective than medical therapy.

How do you assess who is suitable?
DP: Assessing which patients are suitable for DBS is a team-based multidisciplinary procedure. The team typically includes a neurologist, a neurosurgeon, a psychologist and a clinical nurse specialist. The patient needs to have their movements assessed. They need to have a comprehensive medical assessment of their symptoms as well as a test of their response to medication. If they have a good response to a particular drug, that may guide us as to whether they will respond well to the surgery. They also have a brain scan to ensure the brain fibres we are targeting are structurally intact and accessible to the surgeon.

It is also extremely important to establish what the patient’s expectations are from the procedure. What aspects of their symptoms do they wish to see improved? If there is a disconnect between what the patient hopes for and what DBS can provide, it will not be a successful procedure.

What happens after the surgery?
DP: Between two and four weeks after the procedure, after ensuring the healing has gone well, I will switch on the pulse generator and programme in what we feel are the optimal settings for the patient. Then we ask them questions about how they are feeling, their movements, their emotional state. We make adjustments depending on their responses. Conventionally, in the first year the neurologist would see the patient three or four times to check things over and make any necessary adjustments. With a progressive disease like Parkinson’s, as the years pass you would need to adjust the settings to account for the continuing deterioration.

Is DBS a difficult surgical process?
EP: It does require some specialist equipment and it is complex. The challenge is placing the electrodes to within a millimetre of the target. The brain has the consistency of a stiff blancmange and the wire connected to the electrode will bend under its own weight, so you need to get a pliable wire through soft tissue to a specific location with high levels of precision. This represents both an engineering and a surgical challenge. For the procedure, we place the patient’s head into a frame that can hold it securely and position it extremely precisely. I then make a hole a couple of millimetres wide and insert a less pliable probe I can control, which I guide to the target area. This probe creates a track in the brain through which I then feed the DBS wire with the electrode on the end. The procedure is called stereotactic neurosurgery.

Does the patient have a role to play in the procedure?
EP: Historically this operation was done with the patient awake, so we could test if the movement problem went away when we stimulated the electrode. Because of the quality of modern CT and MRI scans, we can now locate the target fibres very precisely and place the electrode accordingly. This means we no longer need to test the electrode as part of the procedure, so the patient can have the whole operation under a general anaesthetic, which is much more pleasant for them.

Are there any side effects?
DP: There can be side effects on speech and some unwanted movement. There can also be effects on the patient’s mood and emotion. We will look for these at the patient’s first pulse generator programming session, and then continue to monitor them.

EP: The nice thing about deep brain stimulation today is that it is reversible. Historically you were deliberately creating a brain lesion in order to jam the signals, and this was irreversible. Today if there are side effects which the patient is struggling with, the electrical settings can be altered, or as a last resort they can be switched off or removed entirely.

Will the range of conditions DBS is applied to expand?
EP: In short, yes. It is a very exciting area for research. We now have the opportunity to study a group of people with brain implants, to record those brain signals. This generates exciting opportunities to increase our understanding of this very complex area. Combined with the real increase in what we can see with the latest scanning technology, we are learning a great deal. This can be seen in the increased success of DBS for some psychiatric disorders. My colleague Professor Tipu Aziz, who is a leader in this field and pioneered DBS in the UK in the 1990s, is doing a trial with anorexia nervosa, which is showing very promising results. I can see this technique expanding to treat other physical and psychiatric conditions.

DP: There is medical literature covering a number of other areas where it could be applied, such as degenerative dementias, cognitive impairment in Alzheimer’s disease, and in the disorders that bridge neurology and psychiatry, like Tourette’s syndrome. But there is not literature establishing proven efficacy as yet.

EP: There is increasing evidence that it can help mitigate some psychological disorders such as obsessive-compulsive behaviour and depression. Research in this area is ongoing, but it is currently available to some patients in certain situations.

Is the mechanism for treating psychological disorders the same as for physical ones?
EP: There is electrical circuitry for thoughts and emotions as well as physical movement, and that circuitry can also malfunction. The actual way in which it impacts on the mental processes is less understood than with the movement conditions, but I recall reading a quote from a neurologist saying “all movement is thought in action”, which points to the close relationship between the two processes.

DP: When assessing a patient for DBS, we screen for psychiatric or psychological issues such as anxiety, depression, impulsive and compulsive behaviours, because we know that DBS can have an impact on this once the pulse generator is turned on. A very detailed assessment is undertaken by a psychologist trained to work with DBS therapy, which contributes to the decision as to whether or not a patient is suitable for the procedure.

Is there much innovation in the field?
EP: There is a lot of innovation, split over several categories. There is innovation in how patients are assessed and selected. For example, they might be given wearable devices to measure their movements, which can be fed into a computer and analysed as part of their assessments. The brain scans are getting increasingly sophisticated—we are able to use a form of MRI scan called diffusion tractography to see the brain pathways and see exactly which fibres we want to target. Some surgeons use robots in the procedure. The devices we use are becoming more sophisticated and miniaturised. My research is involved in developing adaptive stimulators—so-called ‘smart stimulators’.

One area that is really exciting is what I would call neuro-restorative technology. This involves molecular, cellular and biological therapies like stem cells or gene therapy, where you alter the natural history of the disorder. So, you could potentially inject something deep into the brain that might stop the dopamine neurones in Parkinson’s from degenerating, or even actually help them to regrow. Our present stimulation technique does not impact on the rate of degeneration, it just improves the symptoms.

What drew you to this operation?
EP: With a lot of degenerative diseases, there are no treatments available that can profoundly improve someone’s life immediately. The notion that with neurosurgery one can improve function and quality of life straight away is very satisfying, as well as exciting.