Meet our researchers: Professor Ludvic Zrinzo, UCL Institute of Neurology

Optimising deep brain stimulation using MRI

Ludvic Zrinzo is one of the pioneers of MRI-verified deep brain stimulation research and therapy in the UK.

Ludvic is a Consultant Neurosurgeon at the National Hospital for Neurology and Neurosurgery at Queen Square in London, Professor of Neurosurgery at the UCL Institute of Neurology, and Head of the Unit of Functional Neurology.

The team at UCL has transformed the lives of hundreds of patients with chronic neurological conditions including movement disorders and mental health disorders.

 

What is deep brain stimulation?

Deep brain stimulation (DBS) is a surgical procedure that involves the insertion of an electrode into a patient’s brain in order to deliver electric current to a very specific area.

The electrodes are attached to brain pacemakers that are implanted under the skin in the chest. The pacemakers are programmed to deliver electric current to the brain, modulating the abnormal signals that cause the neurological condition.

 

The use of DBS in the treatment of movement disorders - such as Parkinson’s disease, tremor and dystonia - is now well-established. Ongoing research at Queen Square is not only helping to optimise the technique for use in patients with these disorders but has enabled the technique to be extended to patients with other disorders including cluster headache and even mental health disorders.

Research to improve effectiveness and safety 

The team at Queen Square has helped more than a thousand patients over the last 16 years. It is important to note, however, that DBS does not provide a cure for these conditions, but does provide relief from symptoms.

Ludvic and colleagues continue their research to develop and refine the procedure, improving safety and patient comfort. They are pioneers in the technique of using MRI to allow "asleep" DBS, a much more comfortable and less daunting way to undergo surgery than under local anaesthesia. They have also applied this method in patients with other conditions, and have published hundreds of papers, sharing their findings with others working in the field, for the benefit of patients worldwide.

Brain Research UK is proud to support this research, which is leading to real improvements in patient outcomes.

A key area of research is the development and application of more advanced imaging techniques. A technique called MRI connectivity, for example, enables the team to look at changes to the blood flow within the brain as well as physical connections within the brain circuits. These techniques show which parts of the brain are ‘talking’ to one another, and enable the development of very intricate connectivity patterns based on the structure and function of the brain.

These connectivity patterns not only help to determine where to place the electrodes for best effect, but also represent biomarkers that can predict which patients might do well on either medication or with surgery, and shed light on the neural mechanisms underlying the disorders and how they respond to different treatments.

Ludvic explains: “Magnetic resonance imaging is a wonderful scientific tool, which really is better than the best magic, where we can visualise the living human brain without having to open the head. Not only can we use this technique to see the structure of the brain, we can use it to look at the connectivity of the brain, giving us an understanding of the brain circuits involved in health and disease.”

He continues: “If you are using MRI to see where you want to go, rather than relying on an atlas of a cadaver’s brain that was cut up in the 1970s, the surgeon can tailor the operation to the individual patient. Not only can we use MRI to guide us to where we want to go, but we can use it to verify that we have reached the right spot. By collecting information on hundreds of patients over the years, we now have a better understanding of which brain locations provide the best long-term outcome. We no longer need to submit patients to stressful situations where they are awake during surgery."

“This is important because we want to give our patients the very best possible long-term results. Researchers around the globe are realising that there is a good correlation between clinical outcome and the exact anatomical location of the brain electrode.”

Optimum use of MRI techniques provides an alternative mechanism for the surgeons to confirm that they have hit the right spot. This removes the need for patients to be awake during surgery, something that can be very traumatic for individual patients. Some patients will not consider awake surgery, and most patients would choose the "asleep" option if it were available. 

DBS beyond movement disorders

Whilst Parkinson’s disease remains the staple of their work, the team continues to explore and develop the use of DBS in patients with other conditions.

Cluster headache is one condition with which the team has demonstrated success. Cluster headache is a terrible condition. It presents with a very severe stabbing pain, like someone is digging a knife into your eye, and has been described as the worst pain known to man.

Queen Square has the biggest cluster headache clinic in the country, with hundreds of patients with cluster headache referred from hospitals around the country.

Building on previous work, in which increased blood flow to an area of the brain called the ventral tegmental area was recorded during attacks, the team has shown that they can help reduce the frequency, severity and duration of attacks by modulating that part of the brain using DBS. The team has published the largest global series of patients undergoing DBS for cluster headache, showing remarkable results. Although it doesn’t work for everyone, 80 per cent of patients experienced a significant and meaningful reduction in ‘headache load’. Again, this is not a cure - but it provides huge relief to patients who are often at the end of their tether.

Once again, the team has used connectivity mapping to try to understand cluster headache better, and why some patients respond to DBS whereas others do not. They hope that this will lead to even better results going forward. 

Mental health disorders have also been an area of interest for the team.

Tourette syndrome has features of both movement and mental disorders. Patients experience an urge to tic, anxiety builds up, and when they perform the tic, anxiety decreases, only to gradually build up again. Anxiety levels can be so high that individuals can have an almost continuous tic. It can be a very debilitating condition. The team has had significant success in treating patients with severe Tourette syndrome, and are using the same connectivity techniques they have used for Parkinson's and tremor to try to understand why some patients do well with surgery and others do not. Can we understand the disorder better? Can we understand the therapy better? Can we improve outcomes? 

They have also trialled DBS in patients with severe refractory obsessive compulsive disorder (OCD), treating some of the worst patients in the country, and achieving very positive results. In these individuals, symptoms are so crippling that they simply cannot function in society. They can be institutionalised, can struggle to hold relationships, and to stay in control of their life. Obsessive rituals can last for hours, to the point that there is no time left in the day for any sort of meaningful interaction with reality. Physical health is compromised by behaviours caused by obsessive thoughts. DBS has been transformative in five of the six patients who participated in this trial. Once again, the team hasn’t stopped there - there’s a variability in outcome between patients and between different brain targets. Brain imaging suggests that different OCD symptoms can be helped to a greater or lesser extent with DBS at different brain targets suggesting different mechanisms of action. 

What does this research mean for patients?

  • The ongoing research taking place at Queen Square is making DBS safer for those undergoing the procedure, by enabling them to place the electrodes correctly at the first attempt, avoiding the need to make multiple surgical passes through the brain.
  • This also speeds up the surgery, helping to reduce waiting lists so that more patients can be helped. 
  • It is making the procedure more effective by determining the best position for the electrodes in different patients. 
  • It is making the procedure easier for patients by removing the need for them to be awake during surgery. 
  • It is opening up the procedure to a wider range of patients by demonstrating success in relieving the symptoms of conditions such as cluster headache and OCD. 

DBS can transform the lives of people who have struggled for many years with a chronic neurological condition.

Sandra, below, could barely walk by the time she was diagnosed with dystonia in her mid-thirties. Unfortunately, the side-effects of the medication she was prescribed outweighed its benefits in terms of improving her ability to walk. With her walk worsening and eventually needing a stick, Sandra didn’t think her mobility would ever get better.

"I tried to conceal my limp with a skipping motion. I was extremely self-conscious and embarrassed, and lacked confidence. I felt people were staring at me and I made excuses not to walk with anyone."

In 2011, Sandra’s neurologist recommended DBS. Sandra happily agreed, in the hope that it would help her to walk again – and it did!

"I underwent the operation thinking that even a 20 per cent improvement in my condition would be good. At the end of the operation I even walked out. I have not used the stick since!"

 

Read more: Browse our research projects