Nerve stimulation restores some consciousness after 15 years of PVS

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Waves traveling across wire frame of man’s brain (Digitally Generated)

A 35-year-old man who had been in a persistent vegetative state (PVS) for 15 years has shown signs of consciousness after receiving a pioneering therapy involving nerve stimulation, reports The Guardian. The treatment challenges a widely-accepted view that there is no prospect of a patient recovering consciousness if they have been in PVS for longer than 12 months.

Since sustaining severe brain injuries in a car accident, the man had been completely unaware of the world around him. But when fitted with an implant to stimulate the vagus nerve, which travels into the brain stem, the man appeared to flicker back into a state of consciousness. He started to track objects with his eyes, began to stay awake while being read a story and his eyes opened wide in surprise when the examiner suddenly moved her face close to the patient’s. He could even respond to some simple requests, such as turning his head when asked – although this took about a minute

Angela Sirigu, who led the work at the Institut des Sciences Cognitives Marc Jeannerod in Lyon, France, said: “He is still paralysed, he cannot talk, but he can respond. Now he is more aware.”

Niels Birbaumer, of the University of Tübingen and a pioneer of brain-computer interfaces to help patients with neurological disorders communicate, said in the report that the findings raised pressing ethical issues. “Many of these patients may and will have been neglected, and passive euthanasia may happen often in a vegetative state,” he said. “This paper is a warning to all those believing that this state is hopeless after a year.”

The vagus nerve, which the treatment targeted, connects the brain to almost all the vital organs in the body, running from the brain stem down both sides of the neck, across the chest and into the abdomen. The report says in the brain, it is linked directly to two regions known to play roles in alertness and consciousness.

In surgery lasting about 20 minutes, a small implant was placed around the vagus nerve in the man’s neck. After one month of vagal nerve stimulation, the patient’s attention, movements and brain activity significantly improved and he had shifted into a state of minimal consciousness. Recordings of brain activity also revealed major changes, with signs of increased electrical communication between brain regions and significantly more activity in areas linked to movement, sensation and awareness.

Similar stimulation has already been shown to help some patients with epilepsy and depression, the report says.

Sirigu and her team now hope to apply the same technique to patients with less serious brain injuries, where even more substantial improvements might be possible. There may even be patients, she said, whose cortex (the part of the brain used for cognitive tasks) is intact, but who have brain stem injuries that have led to limited awareness or consciousness.

The report says the findings offer hope to the families of patients in PVS that it may one day be possible to re-establish some basic form of communication. However, some might also question whether such patients would wish to be made more acutely aware of being in a severely injured state.

I cannot give answer to this question,” said Sirigu. “Personally I think it’s better to be aware, even if it’s a bad state, to be conscious of what’s happening. Then you can have a decision if you want to go on or if you want (euthanasia).”

Damian Cruse, a cognitive neuroscientist at the University of Birmingham, described the findings as “pretty exciting”, adding that in future it might be possible to combine vagal nerve stimulation with other forms of rehabilitation. “If you can just push the patient over the threshold so they can start responding to external stimulation you can maybe help them follow speech therapy and get them to a level where they can start to communicate,” he said.

During the past decade, scientists have made major advances in communicating with “locked in” patients using various forms of brain-computer interface. These have allowed paralysed patients, some of whom had been assumed to be in PVS, to answer “yes” or “no” to questions to let their family and friends know their wishes and their state of wellbeing.

Summary
Patients lying in a vegetative state present severe impairments of consciousness [1] caused by lesions in the cortex, the brainstem, the thalamus and the white matter [2]. There is agreement that this condition may involve disconnections in long-range cortico–cortical and thalamo-cortical pathways [3]. Hence, in the vegetative state cortical activity is ‘deafferented’ from subcortical modulation and/or principally disrupted between fronto-parietal regions. Some patients in a vegetative state recover while others persistently remain in such a state. The neural signature of spontaneous recovery is linked to increased thalamo-cortical activity and improved fronto-parietal functional connectivity [3]. The likelihood of consciousness recovery depends on the extent of brain damage and patients’ etiology, but after one year of unresponsive behavior, chances become low [1]. There is thus a need to explore novel ways of repairing lost consciousness. Here we report beneficial effects of vagus nerve stimulation on consciousness level of a single patient in a vegetative state, including improved behavioral responsiveness and enhanced brain connectivity patterns.

Authors
Martina Corazzol, Guillaume Lio, Arthur Lefevre, Gianluca Deiana, Laurence Tell, Nathalie André-Obadia, Pierre Bourdillon, Marc Guenot, Michel Desmurget, Jacques Luauté, Angela Sirigu

 

 

“We were very happy when we saw him reacting,” says Sirigu. “This patient is like our baby. We are very attached to him. He’ll always remain in our hearts, because he’s our first patient.”

The New Scientist reports that Sirigu and her colleagues chose the 35-year-old man to be the first to trial vagus nerve stimulation because his condition had not improved for 15 years. They reasoned that any improvements in his behaviour would be down to the stimulation and not simply chance fluctuations.

Before the stimulation started, the man was unresponsive, and his eyes were shut for most of the day. If open, they would stare into empty space, says Sirigu. “You had the feeling he was not looking at you.” That changed once her team began stimulating his vagus nerve. Almost immediately, he began opening his eyes more often. About a month after stimulation began, his behavioural improvements started stabilising.

“His eyes were moving around as if he wanted to follow me,” says Sirigu. He then began to respond to instructions to turn his gaze from one side of the bed to another. When a clinician asked him to smile, he’d react by raising his left cheek.

The report says when the team played some of his favourite music by French singer Jean-Jacques Goldman, the man had tears in his eyes. Sirigu says vagus nerve stimulation activates the neuro-endocrinal system, which can explain the tears. But it happened at the same time as he listened to his preferred music, says Sirigu. “What can we say? We can conclude that there was an emotional reaction.”

Sirigu also believes that she startled her patient when she suddenly brought her face close to his. “His eyes were wide open,” she says, suggesting that he was aware of a threat to his personal space.

The man’s mother reported that he would stay awake for longer after the stimulation started. He seemed to be paying attention when his therapist read him a book, because his “eyes were open and oriented”, says Sirigu.

“I’m very thankful to this patient, and thankful to the family, to the mother,” she adds. “It was not easy to have surgery, without knowing what the result would have been. It was a very bold decision for the family.”

 

The Guardian report
Current Biology abstract
New Scientist report


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