‘Smart’ brain stimulation a sea change in management of Parkinson’s

This summer marks a milestone in the treatment of Parkinson's disease in Ireland as deep brain stimulation (DBS) surgery, which is used to treat some of the most debilitating symptoms of the condition, becomes available in the Republic for the first time.

Prior to this, patients had to travel to the UK or Northern Ireland for the procedure but now suitable candidates can have their surgery performed at Beaumont Hospital by consultant neurosurgeon Catherine Moran.

Parkinson's is a neurodegenerative disorder affecting more than six million people worldwide and more than 10,000 in Ireland. Patients with movement disorders such as dystonia, where the muscles contract involuntarily, and Parkinson's tremor respond well to DBS and about 80 per cent of those referred to the national DBS service, which is led by consultant neurologist Prof Richard Walsh at the Mater hospital-based Dublin Neurological Institute, are living with Parkinson's disease.

DBS lessens the stiffness, slowness and tremor symptoms typically associated with the condition and it is activated through electrodes in the brain connected to an implantable pulse generator (IPG). The IPG is like a cardiac pacemaker and is similarly inserted under the skin. Leads are placed on both sides of the patient’s brain and connected to the IPG via a wire that runs down behind the left ear and into the chest. Each lead is programmed to be patient specific and to deliver tiny pulses of stimulation to help control involuntary movement.

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Three stages

“There are three stages to DBS,” Walsh explains. “The first is assessing the suitability of someone for the procedure. It’s not like a tablet where you can give it a try. DBS involves brain surgery and that’s not something you undertake lightly. The second stage is the implant surgery and the third is programming the system for optimum outcomes. Being able to do all three stages in Ireland will give the best possible result, while repatriating DBS cases also represents significant savings for the exchequer.

“DBS surgery is highly skilled,” Walsh adds. “It’s like someone standing at the top of a big oak tree with a javelin and trying to hit a ball at the base of the trunk without touching any of the branches on the way down. Touching the ‘branches’ could cause a disabling bleed. DBS has eight contact points to target different points within the brain and we have to determine which contacts produce the best results when turned on. One of the most rewarding aspects of this surgery is that we have someone who comes in with very severe Parkinson’s symptoms and by slowly introducing the stimulation, the tremor melts away in front of you.”

DBS can be life-changing for those living with Parkinson’s, who often follow a rigorous drugs regime that requires taking medication every three hours. “The problem with oral medication is that it has to run the gauntlet of the GI tract and it wears off, leaving patients unable to move for long periods of time,” Walsh says.

“DBS effectively reboots their system, enabling them to keep going and remain independent. DBS is not a cure for Parkinson’s, because other associated problems will develop over time, but it’s a very effective of controlling one of the most distressing symptoms.”

DBS can be life-changing but it is not perfect. There can be side effects (such as an impact on speech) and getting the balance between stimulation and medication right is tricky. The stimulation can be tweaked, but once it’s set it constantly runs at the same level. In an ideal world, DBS would be more flexible and would self-adjust according to individual need over time. For example, Parkinson’s patients can experience “freeze” moments where they can’t move forward. A little extra stimulation at that point would help.

‘Smart’ DBS

A "thinking" DBS system might sound aspirational but it's actually within sight due to the work of Prof Madeleine Lowery of the School of Electrical and Electronic Engineering at UCD who has been collaborating with Walsh over the past two years.

“We are working on a computer model of the neuromuscular system that shows how DBS affects surrounding brain tissue and the muscles it controls,” Lowery says. “Understanding these characteristics will help inform what stimulation ‘dosages’ are likely to be most effective. Our aim is to develop ‘smart’ DBS that can work out the correct levels of timely stimulation for itself. This will also help prolong the battery life of the IPG and minimise the need for invasive surgery to replace it.

“With existing DBS it is possible to inadvertently stimulate regions of the brain you don’t want stimulated, for example, areas involved in speech,” Lowery adds. “To learn more about this and how it can be overcome we are modelling where a patient’s electrodes are, their brain structures and how the DBS voltage spreads in the surrounding tissue. With this information it can be tuned to a more selective region.”

One of Lowery’s main research areas is motor control and about 15 years ago she became interested in the then emerging field of DBS to treat Parkinson’s. “A lot of the methods I had been using to model muscle activity and electrical stimulation could also be used to better understand DBS,” she says. “We know it works very effectively but it’s not fully understood how, what structures in the brain it is stimulating and how it’s giving its therapeutic benefit.”

Lowery says existing DBS operates within a wide range of stimulation parameters and choosing the right combination for a patient is complex. “You can choose how strong the pulses are, their frequency and how long they last and each can have a dramatic effect on symptoms and any side effects,” she says.

“With computational models we can build a picture of the brain and of the tissue around the electrode and can look at how changing the parameters affects the region of tissue being activated. We can also see the impact on the behaviour of the neurons or nerves within these circuits. So, we can trace the effect from the electrode that stimulated the brain tissue to the networks of neural circuits in the brain to how they affect muscle activity that could show up as Parkinsonian tremor.”

Trial and error

As of now, setting the stimulation pattern still involves trial and error. What Lowery is aiming for is closed-loop or adaptive DBS that can both sense and stimulate. “If we have particular biomarkers that are an indicator of symptoms or side effects and we can automatically sense them then we can adjust the stimulation parameters to give the right type of stimulation at any instant in time,” she says.

“What we’re investigating now is different types of algorithms for controlling the stimulator. We want to be able to embed a smart algorithm in the device that can sense the biomarkers, interpret them and adjust the stimulation parameters accordingly,” she adds.

They already know about some of the biomarkers associated with the electrophysiological symptoms of Parkinson’s, such as difficulty starting a movement and an excess of synchronous neural activity. With Parkinson’s disease groups of neurons become overly synchronised at particular frequencies and lose the ability to communicate properly.

Lowery expects to see aspects of her research applied within a clinical setting within five years. “There are still some open questions but computer modelling will help answer them,” she says. “DBS is primarily used for Parkinson’s but it does have other potential applications for conditions such as OCD, essential tremor disorder and obesity.”