The mystery of shivers

Through a series of groundbreaking studies aided by selfless horse owners, a researcher is beginning to understand this rare but devastating neurological condition.
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Through a series of groundbreaking studies aided by selfless horse owners, a researcher is beginning to understand this rare but devastating neurological condition.

Stanley had been off the track about five months when Kati Johnston first met him. The handsome gray gelding had raced under the name Wild Delight, but by the time he was 5 years old, his potential as an event horse was recognized by some of the biggest names in the sport. He was plucked from the track by famed horseman Bruce Duchossois and sent to the barn of eventing superstar Phillip Dutton, where Johnston worked.

shivers-still

Johnston, in need of a new mount to develop for advanced-level competition, purchased Stanley even though he had one clear physical problem. “He had shivers even back then,” says Johnston. “They were minor, but definitely there.”

At the time, Johnston identified shivers as most horsepeople do---a reluctance to have a hind hoof lifted and held up by a handler. “At that point, he’d let me pick a hind hoof up but only for a few moments, and then he’d pull away in an almost panicked way.”

Stanley’s otherwise wonderful ground manners led Johnston to conclude that his hind-hoof issues weren’t behavioral. “It was clear he wasn’t just being a jerk,” she says. “Something about having his hoof lifted was so difficult that it upset him.” Farrier visits required sedation and patience.

Getting out of a trailer was also a problem. “He’d panic if he had to step backward out of a trailer,” says Johnston. “He’d load like a dream and walk forward down the ramp of Phillip’s large van just fine. But if he had to back out, it was an issue. It didn’t matter if it was a ramp or a step-up; it was like he just couldn’t figure out where to put his feet while moving backward, and he’d fly out in a panic.”

While being ridden, however, Stanley had no troubles---he and Johnston quickly worked their way up the ranks of elite eventing. In three short years, they were readily handling advanced courses and clearing imposing obstacles. “He was a fabulous, fabulous horse to ride,” says Johnston.

The shivers, however, worsened with each passing year. “Eventually it took us 10 minutes per hind hoof to put studs in before we’d go cross-country,” says Johnston. “But there was still no problem riding him. Jumping, lateral work---it was all easy to teach him and easy for him to do. If you watched him under saddle you’d never know he had a problem.”

Beyond a brief, one-year stint with another advanced-level event rider, Stanley remained under Johnston’s care for the next decade, either taking her around courses, being leased to a student or enjoying the occasional off-season while Johnston’s family grew. Eventually, however, his shivers became significantly worse. “He’d lift his foot up and it was like he didn’t know how to put it back down,” she says.

Stanley’s veterinarian had always been aware of the gelding’s shivers and had offered advice to Johnston over the years for managing it, but now he was able to offer a bit more. A prominent researcher, he said, had recently launched a large-scale study of the disorder and might have some insights. He passed along the name and contact information of Stephanie Valberg, DVM, PhD, at the University of Minnesota.

Defining a disease

For years, Valberg had been studying muscle disorders, primarily polysaccharide storage myopathy (PSSM), a genetic disease that causes abnormal accumulation of sugars in the muscles, leading to tying-up-like signs such as stiffness and cramping. “I kind of backed into studying shivers,” says Valberg.

Although PSSM affects mostly stock breeds and draft horses, Valberg would often hear from owners of warmbloods and Thoroughbreds, asking if their horse’s difficulties lifting their hind legs could be a sign of, or somehow related to, PSSM. “Basically, horse owners started asking questions we couldn’t answer,” she says.

Valberg first turned to data she had collected regarding PSSM. “We had biopsied 130 Belgian horses. About one-third of them had type-1 PSSM [caused by a genetic alteration in the glycogen synthase gene], and about one-third had shivers, as reported by their owners or veterinarians. Looking closer, we found that two-thirds of the ones who had shivers didn’t have PSSM. Since there was no direct correlation, we realized we were probably dealing with a separate issue.”

Intrigued, Valberg scoured the veterinary literature for information about shivers and found no consensus on exactly what it was. “If you look through all the textbooks, you find astonishingly different definitions of shivers,” she says. “And even veterinarians will vary widely in how they describe the disease. The reason for that, I think, is because individuals see such a small number of cases, they don’t have much context or reference. That’s when I realized we needed a whole new approach to look at a rare disorder like this.”

For the first phase of her research, Valberg turned to a group that would likely have the most firsthand experience with shivers---owners of affected horses. “We designed an online survey for owners---this was in 2008 and one of the first web-based epidemiologic studies in horses---and we put the word out through colleagues, magazines and websites.”

Eventually, 300 owners took the survey, a response that astounded Valberg. “I’m the first person to throw a survey in the garbage,” she says. “But these 300 horse owners, literally, from all around the world helped us. Without them, we’d have nothing.” The response also helped the research group secure funding by illustrating that even a relatively rare condition can have a profound impact on a population of horses and that work was needed to find a cause and cure.

The original survey asked for a description of each horse’s movement but, says Valberg, “within getting the first few answers we realized that if we were going to study movement, we were going to have to see it. So we began asking for video of each horsegoing through a standardized series of movements---walking forward, turning sharply one way, then the other, backing up, then picking up the legs.”

Videos began coming in, and a graduate student, Alex Draper, organized the submissions for scientific evaluation. “It was a daunting task, particularly in the relatively early days of technology, but we ended up with 70 videos that we were able to include in our studies.”

The videos revealed some clear patterns: “We found that most of the horses had difficulty picking up their hind limbs when asked by a person, as if they were going to pick out the hoof,” says Valberg. “They would hesitate and resist and then when they did pick it up, it would almost hover and shake.” Interestingly, nearly all of the horses had no difficulty lifting their hind limbs naturally when asked to walk forward.

This information provided an important distinction: Shivers was different from stringhalt, another motion disorder of the hind limbs. In stringhalt, the hind legs jerk up toward the belly with each forward step, when the horse is led as well as ridden under saddle. A horse with stringhalt returns the leg to the ground normally after it jerks upward and has less of a problem lifting a hind leg to have his hoof picked out. “It looks very different than shivers, and we were able to determine early on that the two were most likely not related,” says Valberg.

The videos also revealed that there were two basic types of shivers cases. “Some horses refused to back up in hand or lift their legs when asked,” says Valberg. “Their legs would stretch out behind them rather than move upward. Others would pick the leg up just fine but then seemed to have trouble setting it back down again---it would just remain flexed as if they couldn’t put it down. We realized that we were dealing with two variations of shivers---hyperflexion and hyperextension. “

A paper published by Valberg’s team in 2014 describes these two primary types:

• Shivers, hyperextension: “Hyperextension of hind limbs when walking backward with normal for--
ward walking or intermittent mild hyperflexion.” These horses, the researchers note, “extended both forelimbs at the initiation of backward walking which, when combined with hind leg hyperextension, resulted in a stretched sawhorse appearance … horses did not coordinate fore- and hind-limb movements and became reluctant to back, with [most horses] being unable to complete more than two or three strides backward.”

• Shivers, hyperflexion: “Normal forward walking with signs of hind limb hyperflexion when walking backward and manually lifting the hind limb. During hyperflexion, the hind limb was abducted and the affected limb would pause in the hyperflexed state before quickly returning to the ground. Manual lifting of a hind limb was resisted and induced hyperflexion in the opposite hind limb or eventually the hind limb being handled.”

The researchers also identified a third, smaller group of horses with “Shivers, forward hyperflexion.” These horses had abnormal flexion of both hind limbs while walking backward and also intermittently when walking forward. “These were horses with a long history of shivers,” says Valberg. “What had been intermittent became consistent over a period of about three years. These horses had trouble walking if they had any disruption, such as having to turn sharply, and could not lift their hind hooves when asked. These are the horses who end up having to be euthanatized because their legs would get stuck in flexion and they could not move forward, causing panic. When they eventually released the flexed limb they slammed the limb to the ground, which was quite dangerous.”

The survey also provided other data about the horses. “We learned that horses aren’t born this way,” says Valberg. “They all developed these signs over time---some as early as 2 years old, but most not until after age 5. Usually by the age of 10, if a horse was going to have shivers, the signs were there.”

The researchers were also able to develop a profile of horses who are more likely to be affected by shivers. For starters, they tend to be tall. “What we found was that almost every horse with shivers is 16.3 hands or taller,” says Valberg. “There is a strong predilection for height, even more so than breed, although the typically taller breeds like Thoroughbreds, warmbloods and drafts were those most represented.”

Gender also seems to be a factor in susceptibility to shivers. Geldings are three times more likely to be affected than mares. ‘That might be related to height,” says Valberg. “But it could also be that estrogen has a protective effect against the disease process. There’s evidence in humans that estrogen protects a person from certain neurological conditions.”

Searching for an explanation

Now armed with a clearer definition of shivers, and a better picture of which horses might be affected, Valberg’s group turned their attention to finding a cause for the condition. “There are any number of reasons horses don’t want to hold their hind legs up,” she says. “They can have hip or hock issues, an injury or arthritis. But these horses were oftentimes very athletic and otherwise coordinated and sound. Many were functioning at extremely high levels of dressage and show jumping.”

Watching the submitted videos, the researchers were struck by how the horses seemed to be unable to place their feet where they wanted them to go. “In many neurological diseases, such as EPM, horses can’t keep track of where their limbs are in space. This is called a proprioceptive deficit,” says Valberg.

“However, these horses with shivers seemed to know exactly what they needed to do with their hooves, but they just couldn’t do it. It didn’t look like pain, weakness or incoordination, but more like confusion, frustration and even fear. This made us wonder what was going on in the cerebellum, which is the part of the brain that controls muscle memory.”

The cerebellum is the region of the brain that coordinates voluntary motor movement. “When the conscious part of your brain says, ‘I’m thinking about a movement,’ the cerebellum helps coordinate it all. It supplies the information needed for the correct pattern of muscle flexion and extension to make the movement smooth,” explains Valberg. “But if it can’t supply that pattern, the muscles don’t fire properly, and you get the prolonged flexion or extension that doesn’t release, like we see in shivers. Essentially, the brain is saying ‘I know what you want me to do’ but it can’t make that happen.”

To determine if a malfunction in the cerebellum could cause the movements associated with shivers, the researchers attached external electrodes to the skin over the hind leg muscles of affected horses. “These electrodes detected when muscles were firing,” says Valberg. “We put one on the flexor and one on the extensor. On a normal horse, these muscles fire at opposite times when the horse backs. In a horse with shivers, they fired out of sequence. This is exactly what the cerebellum does; it controls the timing of locomotion.”

The explanation for how a horse can excel athletically, yet not be able to lift a hind hoof or back up on command, goes to the very nature of the cerebellum’s function, says Valberg. “The cerebellum controls learned behavior, mainly,” she says. “Rhythmic trotting or galloping---the very natural movements for a horse
---he doesn’t have to think about. Those movements are controlled at the spinal cord level. But backing or lifting a hoof when asked---that’s learned behavior controlled by the cerebellum. You have to teach a horse how to back up in hand; an untrained, unhandled horse may back up a step or two, but then he turns around to go forward when he can. You have to teach a horse to lift his hoof when you grab it and then relax so you can pick it out, but you don’t have to teach him how to gallop. So that’s why he loses the ability to do one but not the other when a very focal area of the cerebellum is damaged.”

Armed with this theory, the researchers asked owners who had participated in the survey if they’d be willing to donate horses who were going to be euthanatized because of severe shivers. “It’s a huge thing to ask of any owner,” says Valberg. “But these were people who had lived through the heartbreak of watching their horses deteriorate, and they were dedicated to helping find the cause so we might begin to prevent it in other horses. We had people from several states agree to donate their horses
for research.”

Through such donations, Valberg’s group was able to examine the brain, spinal cord and periphery nerves of five affected Belgian draft horses and five warmbloods. These were matched with samples from control horses of the same size and breed for comparison.

“We have an amazingly meticulous neuropathologist in our lab,” says Valberg, “and for two years he examined every inch, even every millimeter in some regions, of each four-foot-long specimen, comparing it to a healthy horse. He also devised a special stain to identify the type of nerve cells, looking for even the slightest abnormalities.”

The effort paid off. “In each affected horse, we found a very characteristic degenerative lesion on one very specific area of the cerebellum,” says Valberg. Some degeneration in this area of the brain is a normal part of the aging process, she continues, but horses with shivers had 80 times more degeneration than clinically normal horses of a similar age. “That’s a pretty significant, and even spectacular, difference,” she says.

Valberg’s team is in the process of publishing these findings---the first definitive cause of shivers to be identified.

Moving toward treatment

The research team sees this as just the beginning of their work. “The next step is looking for a genetic basis of shivers,” says Valberg. “We’ve sequenced the entire genome of affected Belgians, and we are going through terabytes of information to see if we can identify any specific defect.”

Defining a clear pattern of inheritance may be tricky, however. “There’s the affect of gender and height to consider,” says Valberg. “If you’re a mare and 16.3 hands tall, you might inherit the defect but not be affected.”

Height could also influence the disease only indirectly. “It’s possible that height just contributes some ‘noise’ to the system,” says Valberg. “The taller horses have longer nerves, with more opportunities for an electrical input to become less crisp. It could be that being tall just makes the existing genetic defect worse.”

Even as answers on shivers emerge, says Valberg, “the bigger payoff is likely to be what this research sparks for other diseases. We didn’t know anything about these movement disorders when we started. Now we have a start, and a template of sorts to try and sort them out and share information. There were videos we looked at where we all said, ‘What the heck is that?’ There are so many conditions that an individual veterinarian may never see, so they don’t get studied often. But if you can get a group of them together and start to categorize them, you see patterns and open up avenues for finding out what they are. If we can give it a name, we can start working on a treatment and prevention.”

While her group hasn’t specifically studied treatment options for shivers, knowing it is a degenerative neurological disease gives Valberg an idea of where to begin looking. “One thing we’ve found with other neurodegenerative conditions is that the horse may not be getting enough antioxidants and, specifically, vitamin E. Maybe we need to pay more attention to that in tall breeds of horses.”

Until a cure is found, the focus will be on managing horses with shivers. The survey done early in Valberg’s research asked what owners had tried and what they felt made a difference. “They had a tried a lot of things, but one that seemed to slow the progression was keeping the horses active and fit,” she says. “This makes sense in that output from the cerebellum would keep the synapses0active and healthy.”

The survey also found that stress temporarily worsens the condition. “If you transport these horses to a new place or something unusual happens at home, they will shiver more until they settle down,” says Valberg. “This suggests there is an excitatory transmitter that plays a role, and if you can minimize that, the horses will do better.”

The biggest management hurdle, shoeing, is most often managed with medication. “If you are trying to shoe these horses, detomidine seems to work well,” says Valberg. “It dampens the urge for the horse to pull the foot away, but it does make the limb very heavy. Some farriers have adapted slings to help hold up the foot while trimming these horses, and draft horse farriers sometimes use special stocks.”

Stanley’s shivers became more severe after other health problems occurred. “He developed melanomas all over his body over a short period of time,” says Johnston. “And his shivers got much worse.”

Eventually, the melanomas became so large they burst, and the shivers progressed to the point Stanley was no longer able step over the threshold of his stall door. “He would kick out in fear and frustration,” says Johnston. “And that’s not my Stanley at all. He was always such a trouper. It broke my heart to see him so scared and miserable.”

Johnston and her veterinarian began discussing putting Stanley down, when the option of donating him to Valberg’s research came up. “I’d always imagined having Stanley for years and years,” says Johnston. “He was only 17, and horses in my barn live well into their 30s. I was angry that shivers was taking him from me so early, but I also saw an opportunity for him to help other horses.”

Johnston sent Stanley to Valberg, who found the telltale lesion in his cerebellum. “Dr. Valberg told me that what she found in Stanley’s brain was so bad that it helped verify the condition was degenerative, and that it was important evidence,” says Johnston. “It made me feel better knowing that it came from Stanley.”

Even today, two years after he was put down, Johnston makes sure Stanley continues to contribute to the cause by sharing her story with others. “I don’t currently know many horses with shivers, but I’m happy to talk about it. People might be hesitant to bring it up because they think it’s a tough subject for me, but it’s the opposite. I want to talk to as many people as I can. Maybe I can share with them something about Stanley that can help their horses.”

This article first appeared in EQUUS issue #448, January 2015.