An 'awakening' moment: sleeping pill restores function to brain-injured patient

Originally published on October 10, 2020.

A man in the Netherlands, who had not been able to move or talk, experienced "spectacular" but temporary "awakening" after treatment with an ordinary sleeping pill, according to a new case study.

Reported in the journal Cortex, neurologists used brain scans to help understand the awakening event, and now have great hopes that they can develop a more durable treatment to help him, and possibly patients suffering from similar ailments.

According to physician and researcher Dr. Hisse Arnts, the patient's story began eight years ago. The man, then in his late 20s, was out for dinner with friends and choked on a piece of meat. He suffered a heart attack and oxygen deprivation resulting in a significant brain injury. 

A rare neurological disorder

The damage to his brain resulted in a rare condition known as akinetic mutism. 

"That means that he is awake, though not aware of his situation and has the inability to move and speak spontaneously," said Arnts, a neurosurgery resident from Amsterdam University Medical Centre. 

"He cannot eat, and he is seemingly indifferent to thirst, pain, hunger and displays no emotions. He's not in a coma. So it's not a disorder of consciousness, but rather a disorder of diminished motivation. He doesn't have the drive to eat, speak or move," said Arnts.

The case intrigued Arnts' colleague, Dr. Willemijn van Erp, physician and researcher from Radboud University Medical Centre in the Netherlands. 

Van Erp had been studying how some coma patients could experience a change in their state with the administration of a commonly prescribed sleeping drug called zolpidem. She approached the man's family and asked if she might try the drug on him.  

"When we first administered the zolpidem, nothing happened. Dr. van Erp went on her bicycle to see the next patient in another nursing home when she was called by the nurse telling her that she had a special person on the line for her. And that special person was, of course, our patient," Arnts told Bob McDonald, host of Quirks & Quarks.

Speaking for the first time in eight years

Although confused, and not quite sure who he was speaking with, the patient was indeed talking for the first time in eight years. While he had some cognitive deficits as a result of his injury, he was able to call his family, and to get up and move around with assistance, according to the study. 

Video: Dr. Willemijn van Erp and the patient in this before and after video

However, this awakening lasted only for about two hours before he began to relapse into his state of akinetic mutism. Over the following weeks, the medical team tried to find a drug regime that would maintain his improved condition, but the drug worked less and less frequently. Eventually two to three weeks elapsed before a dose of the drug would work to awaken him.

"We actually only administered zolpidem on special occasions such as his birthday or dentist appointments or family visits," said Arnts.

Arnts and colleagues were able to investigate what was happening by using electroencephalogram (EEG) and magnetoencephalogram (MEG) technology to measure patterns of brain activity. 

"What we saw, to our surprise, is that there was an extreme overexpression of certain brain waves or overactivity in the brain without the zolpidem," said Arnts. "And this overactivity created noise that prevented motor function and speech to occur. We saw that zolpidem actually reduced these overactivities such that the hidden brain function that was there could reoccur."

Arnts described it as being akin to a symphony orchestra, in which too much volume from the violins drowns out all the other instruments and disrupts the careful coordination between the musicians. In this case, the drug restored the brain's coordination, and the music began to play.

A more permanent solution

Encouraged by their success with the drug and informed by what the patient's brain waves were showing, Arnts said the team has now developed a different strategy to achieve the same effect.

In research yet to be published, the team was able to quiet the inappropriately noisy parts of the brain in the patient with deep brain stimulation. This treatment uses implanted electrodes that can send signals deep into the brain to influence its activity, and in this case duplicate the effects of the sleeping drug.

"We performed deep brain stimulation on this patient a couple of months ago," Arnts said. "And he is already showing some remarkable improvements in motor function. He can now permanently walk with a walker, and he can also eat his favourite food again. So the sleeping pill isn't necessary anymore because he is regulated to another level of awareness right now."

Arnts stressed that the success with this single patient may not be duplicated in other patients with akinetic mutism, let alone other brain injuries or disorders. But there is some good reason to believe this may work with other patients.

"I'm hopeful. It's my strong belief that there are more patients out there with this kind of overactivity in the brain."

And even if the treatment doesn't work, he said it's possible to learn from failures as well as successes.

"I think learning why a patient responds and why others don't is the first step to learn more about steps that are necessary in the future for new therapies."