VALLEJO, California. – The adolescent patient grew grumpy and withdrew. He hadn't eaten in 13 days. Treatment with steroids, phenobarbital, and valium failed to relieve symptoms of his epilepsy. Then, on September 18, he had a terrible fit – he tore his fins violently and passed out in the water.
Cronutt, a 7-year-old sea lion, had to be rescued to keep him from drowning. His vet and the Six Flags Discovery Kingdom caretakers began discussing whether it was time for palliative care.
"We tried everything," said Dr. Claire Simeone, Cronutt & # 39; s longtime veterinarian. "We needed more extreme measures."
On Tuesday morning, Cronutt underwent groundbreaking brain surgery to reverse epilepsy.
If successful, the treatment could prevent an increasing number of sea lions and sea otters from succumbing to a new epilepsy plague. The cause is climate change.
As the oceans warm, algal blooms have spread more widely, forming toxins that are ingested by sardines and anchovies, which in turn are ingested by sea lions, damaging the brain and leading to epilepsy. Sea otters are also at risk from consuming toxin-laden shellfish.
The animals stranded on land received support, but often die. Cronutt can change that.
"If this works, it'll be big," said Mariana Casalia, a neuroscientist at the University of California at San Francisco who pioneered the techniques that led to a procedure at a veterinary center in Redwood City, CA.
This procedure was performed by three neurosurgeons at U.C.S.F. that normally operate on humans. During surgery, they drilled a small hole in Cronutt & # 39; s skull, inserted an ultra-thin needle into the hippocampus of the sea lion's brain, and then implanted embryonic brain cells extracted from a 35-day-old pig. These so-called "inhibitor cells" suppress the electrical activity in the brain that leads to seizures. This process was led by Scott Baraban, a professor of neurosurgery who heads the laboratory where Dr. Casalia works, identified. For over a decade, their technique has been shown to be effective in curing epilepsy in mice.
Cronutt, the first higher mammal to receive treatment, stepped out of surgery and anesthesia at noon and breathed on its own, a first step. It will not be known for several weeks whether the operation will successfully reverse his condition.
Pig cells are important because they have characteristics of higher mammalian species, including marine mammals that have epilepsy. And sea lions and sea otters are increasingly at risk of the disease.
The well-documented phenomenon, first discovered in 1998, led to an increase in sea lions beaching in 2002, another increase in 2015 and annual summer beaches. Thousands of sea lions have now been poisoned by the venom domonic acid. It depletes inhibitory cells that normally help balance excitatory cells in the brain's electrical system. When these cells are out of whack, seizures occur.
The same phenomenon has resulted in the shutdown of the crab fishery to prevent people from eating domonic acid laden crabs and suffering from a disease known as amnesic shellfish poisoning.
In sea lions, scientists have used brain imaging to document how the toxins also break down a part of the brain called the hippocampus, which is involved in memory, navigation, and other functions. When sea lions appear on the beaches of the Pacific coast in the summer, some exhibiting seizures are saved and supported, but they often die.
Researchers first spotted Cronutt after he ran aground in San Luis Obispo, California, in November 2017 and ran into a parking lot that was classified as a "traffic hazard". He didn't seem sick. They marked him for future reference and released him a few weeks later.
Shortly after, a little further north in Marin County, he was identified on a beach where he went to several apartment buildings and climbed porches and tables. This time he went back to the water and a week later was found disoriented on Ocean Beach in San Francisco. "It was reported that a member of the public tried to feed him a burrito," according to a written chronology from Dianne Cameron, director of animal care at Six Flags Discovery Kingdom
Ms. Cameron would eventually become his caretaker after Cronutt – named for the pastry that is a croissant and donut combo – reappeared on a beach in January 2018, this time in Sonoma County. He stood in front of a public bathing area and blocked the entrance. Shortly thereafter, he was classified as unsolvable at the Marine Mammal Center in Sausalito, California for not eating and for having surfaced ashore several times. Then he had a seizure with grandmothers.
The researchers couldn't find a zoo house for the damaged animal. The National Sea Fisheries Service called Ms. Cameron at Six Flags and asked if she would accept him, as the park has rescue facilities and a history of adopting animals with medical problems. She didn't hesitate.
"He's such a cute boy," she said. At Six Flags, he didn't perform like most other marine mammals, like the Pirate, a seal, or the 500-pound Wyland and Shark Bite, both sea lions. Cronutt had recurrent seizures and intensified and more frequent cycles in which he stopped eating for a while and became particularly inattentive, a behavior that the vets attributed to damage to his brain. His weight fell from a high of 255 to 175 pounds.
After his last terrible fight on September 18, Ms. Cameron "went home and prayed that he would make it through the night."
In the days that followed, she and Dr. Simeone to discuss whether it was time to put Cronutt to sleep.
"Then my husband said: You have to call Scott!" Said Dr. Simeone.
Her husband, Dr. Shawn Johnson, also a veterinarian, was referring to Dr. Baraban, the researcher at U.C.S.F. His lab had previously contacted the couple and the Marine Mammal Center because they knew about the problem in sea lions and felt ready to move up the food chain with their experiments.
Dr. Baraban said that even if the surgery is successful, it would not help people with epilepsy as quickly because of the challenges of using pig cells in the human brain and other factors.
"My immediate hope is to help the sea lions and sea otters," he said.
On Monday, the day before surgery, Cronutt appeared to be entering another difficult phase. His appetite had sunk sharply, even though he had vigorously thrown his red ball and splashed it into the water.
Mrs. Cameron would occasionally approach him with a herring with his seizure medication stuffed in its dead throat. "Come on, Cronutt," she pleaded. But the sea lion just took the fish in its mouth and spat it out again.
The damaged brain tissue seemed to interfere with the signal prompting him to eat. Mrs. Cameron could see a dull hue in his eyes of dark walnut wood, not bloodshot and limp as they sometimes get but threatening.
She pondered the upcoming surgery, the results of which won't be known for 30 days when researchers see if his behavior recovers, as it did with mice and rats in previous work.
"Even if it doesn't work and there is a chance it won't," Ms. Cameron said, pausing and starting to cry before she gathered the ocean needs our attention. "
On Wednesday morning, the day after the operation, Cronutt initially seemed to have no appetite. Then he started barking. Mrs. Cameron approached with food, and Cronutt devoured two pounds of herring during the morning.
“He ate, followed me everywhere, was super engaged and very vigilant. I think he feels really good considering he had a drill in his brain just yesterday, ”Ms. Cameron said. "His eyes look beautiful."