Treatment
Some authors suggest that the precipitating factor preceding episodes of paroxysmal dyskinesia is the most significant component in determining the course of the disease, the underlying disease mechanism (see "Pathophysiology"), and response to treatment. The duration of episodes also appears to have some effect on the disease course and treatment response.
Paroxysmal kinesigenic dyskinesia (PKD)
In many patients with idiopathic paroxysmal kinesigenic dyskinesia (PKD), episodes tend to lessen with age. In addition, the attacks may sometimes spontaneously disappear over time (remission). PKD responds well to therapy with various anticonvulsant medications. For example, the anticonvulsant agent phenytoin (Dilantin®), formerly known as diphenylhydantoin, was one of the first medications recognized as an effective therapy for PKD. Reports indicate that patients may also benefit from treatment with the anticonvulsants phenobarbital, primidone (Mysoline®), valproic acid (Depakene®), or the benzodiazepine clonazepam (Klonopin®). In addition, carbamazepine (Tegretol®), another anticonvulsant agent, has been found particularly effective in most PKD patients. Some patients may also benefit from acetazolamide, which is a carbonic anhydrase inhibitor; combination therapy with acetazolamide and carbamazepine; or treatment with tetrabenazine, a monoamine-depleting agent. Although therapy with the dopamine precursor levodopa (L-dopa) has been effective for some PKD patients, others have not received benefit from such therapy.
Symptomatic PKD, such as that associated with multiple sclerosis (MS) or head injury, may also be relieved by anticonvulsant drug therapy, possibly in combination with other appropriate agents (e.g., acetazolamide). Depending upon the nature of the underlying or primary condition, other therapies may be required to help control kinesigenic episodes. For example, in patients with symptomatic PKD in association with decreased activity of the parathyroid glands (hypoparathyroidism) and abnormal calcium deposits (calcifications) within the basal ganglia, administration of calciferol (ergocalciferol), a vitamin D analog, may help to alleviate PKD episodes.
Paroxysmal non-kinesigenic dyskinesia (PNKD)
The non-kinesigenic episodes of idiopathic PNKD may also decrease in frequency and intensity over time in some patients. However, they often may persist. Unlike PKD, PNKD usually does not respond to anticonvulsant therapy. Yet, in some cases, patients may benefit from treatment with certain anticonvulsants, such as clonazepam, valproic acid or phenobarbital. Indeed, clonazepam (Klonopin®) is often considered the medication of choice for PNKD. Benzodiazepines, a class of medications that act on the central nervous system, may be helpful in relaxing muscles, relieving anxiety, or promoting sleep. Other benzodiazepines also may have some effectiveness in PNKD, such as oxazepam (Serax®) or diazepam (Valium®). Other agents occasionally found effective for some patients include benztropin (Cogentin®), possibly in combination with phenytoin; acetazolamide; carbamazepine; chlordiazepoxide; trihexyphenidyl; dopamine depleting drugs (e.g., tetrabenazine) or dopamine receptor antagonists (e.g., haloperidol). However, it is important to note that some patients report an exacerbation of symptoms when treated with antidopaminergic drugs. In addition, whereas therapy with the dopamine precursor L-dopa has been reported to aggravate symptoms, some patients have received moderate benefit from such treatment. Some researchers suggest that patients with long-lasting PNKD episodes may tend to have an increased response to medication than those with short-lasting attacks.
In addition, in some patients with symptomatic PNKD, administration of appropriate therapies to manage an underlying condition, such as certain endocrine disorders (e.g., diabetes or idiopathic hypoparathyroidism), may alleviate non-kinesigenic episodes.
Paroxysmal exertion-induced dyskinesia (PED)
In some patients with familial PED, the attacks spontaneously remit; others may improve with certain benzodiazepines, such as clonazepam and the anticonvulsant agent carbamazepine. Most patients, however, obtain no benefit from treatment with clonazepam, anticonvulsants, or other attempted therapies (e.g., levodopa, trihexyphenidyl, barbiturates).
Paroxysmal hypnogenic dyskinesia (PHD)
Unlike other forms of paroxysmal dyskinesia (e.g., PKD and PNKD), paroxysmal hypnogenic dyskinesia (PHD) episodes typically do not lessen with age. However, some familial cases have been reported in which episodes spontaneously disappeared with age (remission).
Most patients with short-lasting PHD episodes benefit from carbamazepine. In some cases, other anticonvulsants may also be effective, such as phenytoin (Dilantin®) or combination therapy with phenytoin and phenobarbital. In contrast, according to reports in the medical literature, those patients with long-lasting nocturnal attacks did not respond to anticonvulsant therapy, nor were administration of benzodiazepines or certain antipsychotic agents (phenothiazines) effective. However, a patient with long-lasting PHD secondary to head trauma had an effective response to therapy with the carbonic anhydrase inhibitor acetazolamide.
In addition to medical therapy, surgical interventions such as chronic thalamic stimulation, are being explored as potential therapies in patients with medically intractable paroxysmal dyskinesias.
