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 themselves.

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.

Chorea
Many patients 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
CLASS	MEDICATION	STARTING DOSE	MAXIMUM DOSE	ADVERSE EFFECTS
Neuroleptics                                     Benzodiazepines           Dopamine Depleting Agents	Haloperidol               Fluphenazine   Risperidone   Thiothixene       Thioridazme     Clonazepam       Diazepam   Reserpine     Tetrabenazine	0.5-lmg/day               0.5-lmg/day   0.5-lmg/day   l-2mg/day       l0mg/day     0.5mg/day       1.25mg/day   0.lmg/day     25mg/day	6-8mg/day               6-8mg/day   6mg/day   10-20mg/day     l00mg/day     4mg/day        20mg/day   3mg/day     l00mg/day	sedation, parkisonism, dystonia, akathisia, hypotension, constipation, dry mouth, weight gain   same   less parkinsonism   less parkinsonism, more sedation and postural hypotension   similar to thiothixene   sedation, ataxia, apathy, withdrawal seizures   same   hypotension, sedation,depression   less hypotension

 

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 chorea.

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 l00mg/day.

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.