The lurching is a symptom of the illness, caused by the degeneration of the brain, particularly the basal ganglia, which plays a role in motor function. The movement tics are called chorea, the Greek word for “dance,” but it looks more like a marionette show. Imagine an invisible hand rhythmically pulling your limbs, your head, and even your tongue in different directions. That’s chorea. The tics are involuntary. They don’t hurt—until the end of the day, when your muscles ache from the constant motion.
Losing control of your muscles is only one symptom of Huntington’s disease. You also slowly lose your mind: HD patients have difficulty recollecting words, reading emotions in others, learning new things, and remembering old information. Yet these symptoms appear later. Early on—even before the chorea—researchers have found that the symptoms are often more subtle personality changes. One hallmark of the early disease is a feeling of being uncontrollably annoyed.
Although the symptom is defined as irritability, there is no standard clinical definition of the term. Irritability has been largely neglected by psychiatry, according to neuropsychiatrist David Craufurd of the University of Manchester School of Medicine in the United Kingdom. It’s not particularly well studied, well measured, or even well defined. Although irritability is a symptom of other mental illnesses—Tourette’s syndrome, autism, and personality disorders—Huntington’s disease is one of the few illnesses in which the behavior has been systematically studied.
Understanding the brain changes that occur in Huntington’s patients may reveal something about what triggers people to become annoyed and why some people are more prone than others to be irritable.
For healthy people, irritability could be thought of as a person’s propensity to get annoyed. Craufurd, who has thought about irritability in Huntington’s patients perhaps as much as anyone, says, “In common parlance in England, we say that somebody has a short fuse. Irritability is the length of your fuse, so to speak.”
Another way to think about a short fuse, says Kevin Craig, a psychiatrist based in Cambridge, United Kingdom, is as a lens or a mood. Craig distinguishes emotions from moods. “The idea is that emotions have an object. So, if you’re annoyed or surprised or disgusted, it’s always at something or about something that’s external to yourself.” Surprise, happiness, and anger are emotions. The feeling of being annoyed might fit into the emotion category—it’s often short-lived and prompted by something external. “Whereas with moods, it’s more like a lens or a filter,” Craig says.
For psychiatrists who treat Huntington’s patients, it’s not so much the irritable filter that’s the problem, it’s the expression of the irritability. “As psychiatrists, we don’t deal as much in Huntington’s with the internal state as we do with the external,” says Karen Anderson, who runs the Huntington’s clinic at the University of Maryland. It’s not the patients who complain of feeling annoyed, Anderson says. “It’s the family that sees the external manifestation.”
HD patients with this symptom punch walls and damage property, kick over their children’s bikes, and throw plates at their spouses because dinner was too salty. This is annoyance to the point of dysfunction. This is annoyance as a disease.
Chris Furbee remembers being aware of his mother’s symptoms when he was thirteen and she was in her late thirties. She had movement tics—a subtler version of his grandfather’s swaying. Huntington’s symptoms usually start to appear at this age—around forty. He also remembers his mother acting annoyed: “This is all in hindsight. She seemed to be angry a lot. Back then, I just thought it was my mom being mean. But I think what happened was the disease affected her to the point where she was very irritable.”
Yet Chris says it’s hard to separate the disease from the circumstances. “A lot of that could have been the fact that she was living with her own parents, in this trailer in Philippi, West Virginia—it’s not ideally where she wanted to be,” he says. This is one of the difficulties with measuring irritability as a symptom of a disease. The details of your life make a difference. “It’s easy not to be very irritable if you live in an environment where people don’t impinge on you too much,” says David Craufurd. “Somebody who lives alone, on the whole, tends to be less irritable than somebody who lives with teenage children, shall we say.”
Chris left his mother when he was a teenager. At eighteen, he relocated to the San Francisco Bay area. His grandfather had died. His mom was still driving, showing only mild symptoms, he remembers. He went back a few times, and then years passed without a visit.
Huntington’s is an inherited disease. Your likelihood of having it is written on the short arm of chromosome four. If one of your parents has the disease, you have a 50 percent chance of inheriting it. If you do not inherit the disease, you cannot pass it on—Huntington’s in your family ends with you.
The gene that causes the disease, technically called IT15, holds the instructions for making the huntingtin protein. What, exactly, the protein does is still a mystery, but it appears to play an important role in nerve cell function. The disease occurs when instructions for the protein are screwed up. Specifically, the gene carrying the instructions includes a sequence of repeating base pairs—cyotosine-adenine- guanine (CAG). Ten to thirty-five CAG repeats on that gene is normal. Thirty-six to thirty-nine puts one at risk for developing the disease. Forty or more repeats, and you will get Huntington’s, with no ambiguity in the prognosis. There is no cure or approved treatment for slowing the disease. Most people die fifteen to twenty years after they start to show symptoms.
The problem with the repeats in the instructions is that they cause the huntingtin protein to be built wrong. “It spoils the shape of the protein, and this has a functional effect of some sort,” says Craufurd. If the language sounds vague, that’s because our understanding of how that malformed protein wreaks havoc on the body and the brain isn’t clear. “There are twenty-five different theories about what the problem is,” says Karen Anderson, “but there is no good solid answer as to what is really going on, which is why we’ve had so much trouble targeting it with the treatment trials.”
Although the mechanism isn’t obvious, the effects are: the busted protein somehow causes muscles to waste away. The liver and the spleen suffer, Craufurd says. HD patients burn calories at a rapid rate, “which sounds wonderful until you realize they also have swallowing problems,” says Anderson. “They can’t possibly eat what most of us eat in a day, let alone enough food to burn four thousand calories in a day, which some of them easily can.”
The brain, however, is the main target of the illness. It shrinks. Brain cells die, and the brain atrophies. One area that suffers the most is the basal ganglia—particularly, the caudate, a primitive section buried deep within the brain. The cerebral cortex also thins out, Craufurd says. “It’s really quite widespread. It’s not uniform throughout the brain. There are some areas where there’s more atrophy than others. You can see that cortical atrophy starts quite early.”
Like a domino effect, when one area of the brain dies, the connections from that area to other places die as well. Karen Anderson says, “As a result of the caudate dying, all of these connections to the frontal lobe and other parts of the brain also die off.”