In the focal dystonias, the most effective treatment has proved to be the periodic injection of botulinum toxin into the affected muscles as discussed earlier and emphasized later in the chapter. The acute dystonic drug reactions are treated as noted above. Numerous drugs have been used to treat idiopathic chronic generalized dystonia, with a notable lack of success. Fahn reported beneficial effects (more so in children than in adults) with the anticholinergic agents, trihexyphenidyl, benztropine, and ethopropazine given in large doses—which are achieved by increasing the medications very gradually.
The drug-induced tardive dyskinesias require specialized treatment, as described in later chapters and further on. Tetrabenazine and reserpine, centrally active monoamine-depleting agents, are effective. The offending drug may be at first stopped in patients who have not already ceased taking it, but this often leads to worsening of the movements. Reinstitution of the offending drug or high doses of anticholinergic agents is then sometimes necessary but is only partially effective, and requires that the patient tolerate the other effects of the medication such as sedation and parkinsonism. The problem has become less frequent with the introduction of the newer classes of antipsychosis drugs.
Stereotactic surgery on the pallidum and ventrolateral thalamus, a treatment introduced by Cooper in the middle of the last century, had generally positive but unpredictable results in generalized dystonia. In recent years there has been a renewed interest in a modern derivative of this form of treatment, deep brain stimulation. In a controlled trial, Vidailhet and colleagues demonstrated the effectiveness of this approach by stimulating the posteroventral globus pallidus bilaterally. Their patients had an average improvement of 50 percent on most scores of dystonic movement over 1 year. Increasingly, this is the method resorted to in cases of severe generalized dystonia.
Under the names paroxysmal kinesigenic dyskinesia, familial paroxysmal choreoathetosis, and periodic dystonia, among others, are a number of uncommon sporadic or familial disorders characterized by paroxysmal attacks of choreoathetotic movements or dystonic spasms of the limbs and trunk. Both children and young adults are affected.
There are three main forms of familial paroxysmal choreoathetosis and dystonia. Various genes and mutations have been implicated, some of which involve ion channels. One clinical type, which has an autosomal dominant (less often recessive) pattern of inheritance and a tendency to affect males, begins in adolescence or earlier and abates later in life. It is characterized by numerous brief (several minutes) attacks of dystonia or choreoathetosis provoked by sudden movement, startle, or hyperventilation—hence the name paroxysmal kinesigenic choreoathetosis. There may be many dozens of attacks per day or occasional ones. This disorder responds well to antiepileptic medication, particularly to phenytoin and carbamazepine. Mutations of PRRT2, the proline-rich transmembrane protein, have been identified as the cause in some families and link the disease to a variety of infantile convulsions as summarized by Gardiner and colleagues.
In a second nonkinesigenic type, such as described by Mount and Reback and subsequently by Lance and by Plant et al, the attacks take the form of persistent (5 min to 4 h) dystonic spasms and reportedly have been precipitated by the ingestion of alcohol or coffee or by fatigue but not by movement. The attacks may be predominantly one sided or bilateral. Attacks may occur every several days or be separated by years. A favorable response to benzodiazepines (clonazepam) has been reported, even when the drug is given on alternate days (Kurlan and Shoulson). This form of the disease is inherited as an autosomal dominant trait; a few families have displayed diplopia and spasticity and others have shown a familial tendency to infantile convulsions. There are several variations of this nonkinesigenic illness, each with a different implicated gene mutation.