OVERVIEW The movement
disorder is characterized both by the emergence of involuntary movements, or chorea, and by impairment of voluntary movements.
This latter impairment often contributes more to disability than the chorea itself, resulting in reduced manual dexterity,
slurred speech, swallowing difficulties, problems with balance, and falls.
Both chorea and impairment of voluntary movements progress in the middle stages of HD, but later, chorea often declines
as patients become rigid and unable to initiate voluntary movements. Patients in this advanced state are unable to care for
INTRODUCTION - There are two parts to the movement disorder associated
with Huntingtons disease: the presence of involuntary movements, and the impairment of voluntary movements. The involuntary
movements are called chorea, or choreoathetosis, and consist of irregular jerking or writhing movements. Chorea is the most
noticeable feature of HD. In fact, the condition is often referred to as Huntington's Chorea , yet the impairment of
voluntary movement is more highly corelated with functional disability.
Abnormal eye movements (interrupted pursuit and slow, hypometric saccades), slow and uncoordinated fine movements, dysarthria,
gait disturbance, and dysphagia can be largely independent of chorea and may limit a person's movement disorder, cognition,
or mood. ability to work, care for himself, and communicate.
Although it is tempting to treat the highly noticeable chorea of Huntington's disease right away, it is important to remember
that the drugs used to suppress chorea can have disadvantages of their own, including worsening of voluntary motor disturbance.
TABLE2: PRINCIPLES OF TREATMENT|
OF THE MOVEMENT DISORDER
- Consider non-drug interventions first.
- Pharmacologic treatment of chorea
may worsen other aspects of the
movement disorder, cognition or mood.
- Chorea may diminish over time,
reducing the need fortreatment.
are not bothered by their chorea and may not even be aware of most of the movements. The physician and patient first need
to establish whether the chorea requires any treatment at all. Is the chorea severe enough to interfere with voluntary activities
such as writing, cooking, or eating? Does severe chorea seem to be causing falls or accidents? Is highly visible chorea a
significant source of distress for the patient?
Before beginning medication for chorea, non-pharmacologic interventions should be considered. Chorea, like most forms of
involuntary movement, is worsened by stress, anxiety, or depression, is decreased during sleep, and often
varies with posture or positioning. Treatment of underlying mood and anxiety disorders, and providing a calm, predictable
environment are a first step.
Various assistive devices may be helpful. These include padded, reclining chairs, padding for the bed, and wrist and ankle
weights to reduce the amplitude of the chorea. Sources for some of these devices are provided in Appendix 3.
Doctor and patient also need to have realistic expectations for pharmacotherapy. Medications will not alter the progression
of the underlying illness. They will not improve speech or the ability to swallow, prevent falls, or improve fine motor control.
In fact, drug-related side effects such as sedation and rigidity may increase the risk of falls
and decrease the intelligibility of speech. However, reduction of severe chorea may improve gross motor control and may be
of cosmetic value.
Akathisia is an extremely uncomfortable internal sense of restlessness, sometimes induced by
neuroleptics, which may cause patients to pace, or be unable to sit still. It can be mistaken for agitation or anxiety, prompting
the physician to increase the dose of the offending drug, creating a vicious cycle.
The movement disorder of HD changes over time. In most patients chorea eventually peaks and then begins to decline,
while rigidity and bradykinesia become more significant. At this point, the drugs that helped to suppress chorea may no longer
be needed, and in fact may worsen HD-related rigidity. Therefore it is important to assess the need for anti-chorea
medication at regular intervals, and perhaps to make periodic trials of dose reduction or discontinuation.
TABLE 3: MEDICATIONS USED TO SUPRESS CHOREA|
more sedation and
Three classes of medication are commonly used to suppress chorea in Huntington's disease: neuroleptics,
such as haloperidol and fluphenazine; benzodiazepines, such as clonazepam and diazepam; and dopamine depleting agents, such
as reserpine and tetrabenazine. Each class has its advantages and disadvantages.
The suppression of movement, regarded as a side effect when neuroleptics are used to treat psychosis, is the desired effect
when they are used to treat chorea. Therefore the most popular neuroleptic agents are the high potency drugs, which can also
induce the most parkinsonism.
Haloperidol and fluphenazine are most commonly prescribed. They should be started at a low dose, 0.5 to lmg once or twice
a day, and gradually increased to efficacy. Doses higher than 6-8mg per day have not generally been found helpful in treating
Risperidone is a newer neuroleptic which does not cause as much parkinsonism as the other high potency agents, but is still
useful in suppressing chorea and may relieve agitation as well. It may be also be started at 0.5-lmg once or twice a day,
with some patients tolerating doses as high as 6-8mg daily.
In some cases, patients who experience unacceptable rigidity, akathisia, or dystonia with high potency agents may benefit
from a lower potency neuroleptic such as thiothixene or thioridazine. This may be preferable to adding an anticholinergic
agent to the original drug to counteract the side effects.
Lower potency agents tend to be more sedating, however, and are more inherently anticholinergic, producing more tachycardia,
postural hypotension, constipation, and delirium. Thiothixene can be started at l-2mg once or twice a day and increased to
10-20mg/day. Thioridazine, which is even lower potency, can be started at l0mg once or twice a day and increased to about
Patients starting neuroleptics should be warned about two unlikely, but potentially serious adverse effects.
The first is tardive dyskinesia, a syndrome of involuntary movements
often first noted in the face and mouth, that develops in some patients taking neuroleptics. Tardive dyskinesia is of concern
because the symptoms are usually permanent, and will likely be hard to recognize in someone with HD.
The other serious problem is neuroleptic malignant syndrome, a rare,
but life threatening reaction characterized by acute onset of delirium, rigidity, and fever, often accompanied by leukocytocis,
and elevated CPK. Families should know about this so that the patient can be given prompt medical attention if it develops.
Benzodiazepines, such as clonazepam and diazepam can also be useful in the treatment of chorea. Some clinicians
prefer them to neuroleptics because they do not induce parkinsonism or tardive dyskinesia. Sedation and the increased risk
of delirium are the main deleterious side effects, along with tolerance, withdrawal symptoms, and the potential for abuse.
Long acting varieties such as clonazepam and diazepam are favored because they require less frequent dosing, provide
more even coverage of symptoms throughout the day, and are less likely to precipitate withdrawal symptoms if a dose is missed.
Clonazepam may be started at 0.5mg per day, and may be raised as high as 4mg per day, in divided doses. Diazepam may be dosed
from about 1.25mg to 20mg per day, also in divided doses.
Some clinicians favor dopamine depleting agents as a treatment for chorea. While these drugs do share some of the "neuroleptic"
side effects, they may be milder at low doses, and they have not been shown to cause tardive dyskinesia. The class includes
reserpine and tetrabenazine, which is not sold in the United States, but is used widely in Europe.
Reserpine was used in the past as an antihypertensive, and may cause hypotension. This can be minimized by giving the drug
at bedtime. Parkinsonism, restlessness, dizziness, and sedation are other common side effects. The increased rate of depression
in patients taking these agents is also of concern. Reserpine may be started at 0.lmg per day and increased weekly to a dose
as great as 3mg per day.
Tetrabenazine is similar in action to reserpine, but is felt by some clinicians to be more effective and is less likely
to cause hypotension. It can be started at 12.5mg bid or tid and increased over several weeks to a maximum of 75 or l00mg
per day in divided doses. Tetrabenazine may be obtained from John Bell & Croyden in the UK by calling 011-44-171-935-5555
or faxing a prescription to 011-44-171-935-9605. The drug is costly and probably will not be covered by insurance.