Paolo Sanvito often freezes like a statue after entering the meeting room when he worked as a manager in a multinational company. Known as gait freezing, it is a symptom of crippling Parkinson's disease, a degenerative brain disorder that he suffered.
During the freezing episode, a patient feels like their feet are stuck on the ground for a few seconds or more while they try to take steps. "You can walk or try to stand up from your chair and your body no longer responds to your orders," said Francesco Cecchini, founder and CEO of Gondola Medical Technologies in Switzerland. "Patients can very often fall after a freezing episode."
What's more, when other people are around, the inability to move is more likely and can be more intense. In the case of Sanvito, asking his coworkers to look at him during a meeting will result in more extreme episodes.
More than half of people with advanced Parkinson's disease experience a freezing gait but existing treatments do not work for everyone and have limitations. The drug helps Sanvito, for example, but its effects will disappear so he has to plan his work schedule according to his pill schedule.
In some cases, physiotherapy can also relieve symptoms, especially if combined with cues such as stepping to the side first or determining the time for the rhythm. And deep brain stimulation (DBS) – a procedure in which two electrodes are implanted in the brain and stimulated with electrical impulses – can provide assistance but require major surgery and can cause discomfort.
Better care for gait freezing is needed. AmirAli Farokhniaee, a postdoctoral fellow in the neuromuscular system laboratory at University College Dublin in Ireland, and his colleagues focused on improving DBS as part of the DBS Model project led by Professor Madeleine Lowery. "This can work for gait rigidity but I think we can still make it better because there is a percentage of people who don't get all the benefits of therapy," Dr. Farokhniaee.
The team also wants to make this therapy less invasive. Initially, this could be by using shorter electrodes that do not penetrate as deep as possible in the brain. They also want to see whether adding pauses between pulses rather than constant stimulation can be more comfortable for patients with the same effect.
Gait freezing is difficult to overcome because the brain mechanism responsible for it is still unclear. Some brain regions, such as some associated with movement and anxiety, seem to be involved, as well as brain tissue that fails. For example, it was recently discovered that when healthy people walk, communication between the subthalamic nucleus and the cortex – the two main areas that play a role in mobilization – is synchronized. But during freezing gait, the activity is separated.
Furthermore, how DBS works and why it provides relief to patients is not fully understood. "It's like a technician who changes resistors in a circuit, and he doesn't really know what's happening in the electric circuit but it works," Dr. Farokhniaee.
This therapy usually stimulates the subthalamic nucleus, where the misfiring of neurons is related to problems with movements experienced by Parkinson's patients. However, identifying additional areas involved in gait freezing and other symptoms can lead to new targets.
Therefore the team's first step was to try and uncover how DBS affected the brain by making computer simulations. They mimic therapies in different parts of the brain to see how their activities or functions change. "This is one of the most basic things we have to do," Dr. Farokhniaee. "With simulations, we can improve methods of deep brain stimulation at this time."
Meanwhile, in Switzerland, Cecchini and his colleagues are testing whether stimulating a completely different part of the body – the feet – can improve communication between the body and the brain to treat gait freezing.
Cecchini and his colleagues have developed a portable device, called Gondola, which can be used at home. When attached to the patient's feet, physically stimulate two areas in each leg – the upper part of the big toe and the metatarsal joint further down – for about two minutes. "In most cases, the benefits are immediate and last for three to four days after treatment," said Cecchini.
The device modifies how movement is processed by the brain and spinal cord by increasing messages sent from nerves in the body. By carrying out fMRI brain scans of Parkinson's sufferers, Cecchini and colleagues have also shown that stimulation increases connectivity between the cerebellum, basal ganglia and frontal motor cortex, the three main areas involved in movement. "(Care) is the first of its kind," said Cecchini. " This is truly unique in terms of results and effectiveness. "
Sanvito, for example, happened to find a Gondola device and saw repairs immediately after trying it. "That allows me to return to normal, without the need to increase the dose of my medication," he said.
Cecchini and his team are currently working to improve the device so that it can be linked to a mobile application. This will be able to monitor patients and remind them to repeat the treatment if the freezing gait starts to recur. It will also be able to change remote stimulation settings, which need to be adjusted once or twice a year.
The team is now exploring how the device can be used to help stroke patients as well. The condition, which occurs when blood supply to the brain is disrupted, affects about 15 million people per year worldwide. About 60% of sufferers will have long-term disabilities as a result, such as difficulty walking and balance problems.
The Gondola device can, however, provide a quick fix, using the exact same care used for gait freezing. "From what we have seen so far, stroke patients respond very well to our treatment," Cecchini said. "It's very exciting because we really give people an improvement in their lives."
Network movement 'overload' cycling with Parkinson
Parkinson's Disease: Brain, foot stimulation can help people cope with frozen episodes (2019, 29 October)
taken October 29, 2019
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