Time to Make the Call from Behavioral Symptoms
Thomas Bird, M.D., served as a professor of neurology at the University of Washington for most of his career as a neurologist specializing in neurogenetics. Today, he is officially retired from this role, but active in providing clinical consultation within the Huntington’s disease community.
The time is overdue to expand diagnosis of Huntington’s disease to gene-positive juvenile and pre-manifest (motor) patients based on cognitive, behavioral and psychiatric symptoms — on the right time frame and with the right evidence. From my 45-year perspective, I offer here some history on the evolution of how we have viewed Huntington’s disease, and some thoughts on how we, as researchers and clinicians, can move forward to break through limited thinking that need no longer apply today.
The Strength of the Chorea Bias
Historically, HD was always viewed through the movement disorder lens. For decades and decades, it was called Huntington’s chorea, because the major component of the disease was a movement disorder. This is clear symptomatology, because it marks these people who are demonstrating, before your very eyes, their abnormal movements — you can see it on the metro bus, you can see it on the subway, you can see it on the street corner, saying nothing of seeing it in the clinic.
Yet there was never any doubt that Huntington’s also affected behavior and cognition. If you go back to what George Huntington originally described in On Chorea in 1872, it clearly included psychiatric disease, abnormal behavior. He even mentioned the tendency to suicide. I think this part was somewhat shunted aside because the movement disorder part was so obvious. It is still under the category of a movement disorder in our diagnostic manuals today.
In the 1970’s and 1980’s, people decided we needed to stop calling it by that name, because it’s more than chorea, and some people with HD don’t even have chorea. Seeing the juvenile form helped precipitate that change, as we realized symptoms in these young people can often be rigidity, dystonia, ataxia — but not chorea. And many died of HD before adulthood, so the movement disorder was often never manifest at all.
At that point experts took chorea out of the name and it became Huntington’s disease. But still, the motor manifestations remained the focus. It’s still what you often see when you walk in the clinic door.
Yet I and other HD center neurologists were seeing those patients who had primarily behavioral, psychiatric or cognitive manifestations. Their lives began to crumble and fall apart because they were behaving abnormally, and motor symptoms didn’t always accompany this. When we examined them in clinic, some had no motor manifestations or only very, very subtle ones.
Before the genetic test was available, maybe all one knew was that a patient was behaving abnormally and had a family history. But if they didn’t have chorea, how did you really know they had Huntington’s?
There has been a lot of resistance to making the diagnosis based on these behaviors alone, even when the person is gene-positive. Many will still say, “How do you know it is an abnormal brain causing these problems?” or “How do you really know they aren’t just unhappy, perhaps being raised in a family that is dysfunctional because of a parent’s HD?” So the question was, is it nature or nurture, brain disease or environment?
Why Can’t We Say That?
That knot began to untangle when the genetic test became available in the 1990’s. Then you didn’t have people saying, “Well, you don’t know if they’ve actually inherited Huntington’s or not. They’re acting funny, but there’s a 50/50 chance they haven’t inherited it.” You could at least know with certainty that they had inherited the abnormal genetic mutation.
Since then, say you have a 30-year-old family member who is exhibiting very strange behavior. Maybe they are having delusions, are agitated, or getting into fights. Maybe they are abusing their spouse, or have lost their job, and you know that a parent had Huntington’s.
If they want to know if they’ve inherited it or not, you can do the genetic test. If it’s positive — say they have 45 CAG repeats — at that point we should acknowledge that Huntington’s disease can cause abnormal behavior, just like it may cause chorea. Now you have someone who, one, has inherited the mutation for the disease, and two, has manifestations that we know are related to the disease. So, it is highly likely they are manifesting Huntington’s disease, even though they don’t have chorea.
Often, these behavioral or cognitive changes are some of the earliest manifestations. There was a paper that was published a couple of years ago that said one of the earliest manifestations of this disease in adults is the loss of a job. And that probably represents their cognitive problem. They have problems with multitasking, attention span, and problems with judgment. So it’s not surprising that one of the first things you notice in these people’s lives is that they can’t work anymore.
They can come to your clinic and you can find no movement disorder. Their spouse says their father died with Huntington’s disease. Do you think their losing of the job could have something to do with Huntington’s disease? If you get a positive genetic test, the odds are substantially increased that this person is manifesting Huntington’s disease. You then need to look at their cognition and behavior in greater detail, and it may be appropriate to actually make the diagnosis of manifesting Huntington’s.
The Socioeconomic Fallout from Failing to Diagnose
In this country, not diagnosing this early can be a really substantial socioeconomic issue because the person can’t get Social Security Disability benefits without a doctor’s diagnosis. What needs to be considered is that if the patient has to wait years for motor manifestations, and they can’t get disability income over that period, you’ve done them a big disservice.
If a licensed doctor says this patient has this disease, the Social Security Administration accepts that. What they don’t accept is a doctor stating, “I think they might have it, but I’m not really sure.” So what we need to do is be more specific about the behaviors — has there been a change, has it continued over time, and make those kinds of distinctions more available in a formal way for other neurologists to use in diagnosis.
So it is to everyone’s advantage, I think, to make the diagnosis if you think that the cognitive and behavioral symptoms warrant it. They are the reason why they can’t work. Assuming these conclusions are true, this is a tremendous benefit to the patients to help offset other ways in which they find their lives and their families’ lives unraveling.
Changes from Baseline Reveal the Most
That said, a diagnosis is rarely made from a snapshot. In those who have a positive genetic test, if they have a significant cognitive or behavioral symptom, you probably need to show this in terms of changes from baseline.
Say they were doing their job just fine for five years, but now they become incompetent. Or they were always a really nice person and now they’re agitated, violent and can’t get along with others. Those kinds of changes, if they persist, need to be followed to make the diagnosis of Huntington’s disease.
Another common problem is not demonstrating the abnormal behavior in the clinic. They may be just fine when you’re sitting there talking to them, but you talk to their spouse and the spouse says, “Boy you should have seen them last night! They were all over the place and they were throwing things and they were angry. They never did that before.” The spouse is reporting a change, so if that’s persistent and affecting their functioning, that’s clearly significant.
In juvenile cases, the child may be having trouble in school. Again, you have to know the baseline. Were they a really good student and now they’re having trouble? Is it persistent? Was it just a couple of weeks, or month after month?
A bit trickier to pinpoint is apathy, which is a common behavioral change in Huntington’s, and can be profound. People who were busy, active individuals just stop doing things. It drives their families crazy. How do you measure apathy? Again, you talk to the families to discern, as best you can, if there has been a persistent change from baseline that doesn’t meet the criteria for depression. Depression and apathy seem similar, but are actually different.
Clinician Due Diligence
In the cognitive realm, the question arises, how much decline do you need to decide it is significant and real? You can do cognitive testing, and that can be very helpful. The problem is this requires neuropsychologists, and a lot of communities don’t have these resources. Even when they do, it’s not cheap, and sometimes the patient doesn’t have the resources to cover the cost.
Practically speaking, then, it can be up to doctors, if they can take the time, to do fairly simple cognitive tests in their clinic, and come to a conclusion based on that.
While gathering this input, there is nothing wrong with a doctor saying, “I don’t know. I can’t tell. I can’t be sure.”
In that case, the best step may be to say, “Come back in three or four months and let’s see how things have developed.”
I have said that I think doctors need to be aware that this disease can manifest early in non-motor kinds of ways and can be diagnosed, based on these symptoms and a positive genetic test.
That said, I think it’s reasonable to hesitate when depression is a primary symptom, because depression is so common in the general population. Delusions are not common, but depression is, and these people have lots of reasons for being depressed. How do you know that they’re not just depressed and that it has nothing to do with the onset of the disease? I do think you have to be careful and not make the diagnosis on the basis of depression alone.
Instead, if somebody in an HD family is depressed, you certainly can treat them with an antidepressant, like you would anyone else with depression. They may respond, whether or not they have inherited Huntington’s.
On the Radar
We are missing the importance of these cognitive and behavioral elements in most of the treatment guidelines. The experts have been very cautious about that. The guidelines tend to state that these behaviors can happen and you have to be aware of them, but you should wait for motor manifestations before you really make the diagnosis.
I know of two groups that are struggling with this issue — one is an HDSA committee with Martha Nance, Vicki Wheelock, myself, and several others. Rather than just tweaking current guidelines in some way, they are also creating vignettes for publication that tell the cognitive/behavioral story.
There is another international group led by Herwig Lange in Germany with a similar focus that is trying to come up with their own guidelines for the diagnosis, including an emphasis on cognitive and behavioral changes.
A part of this mission is to get the message out to general physicians, because it’s clear that a lot of these patients don’t see neurologists, particularly not initially. Disseminating this perspective should help Huntington’s families, their physicians, and society as a whole.