Comprehensive treatment of Huntington disease and other choreic disorders
ABSTRACTThe management of choreic disorders presents significant challenges, including identifying the etiology of the disorder, treating and preventing motor symptoms, and managing a range of other neurologic and behavioral complications. Chorea may occur in several neurodegenerative, genetic, or drug-related conditions, and a thorough diagnostic evaluation is needed to identify the specific underlying causes. Some choreic disorders have specific treatable underlying etiologies, such as vitamin B12 deficiency or drug-induced dyskinesia. Autoimmune disorders such as Sydenham chorea may be treated with penicillin, corticosteroids, intravenous immunoglobulin, or plasma exchange. Heredodegenerative choreas such as Huntington disease often respond to treatment with tetrabenazine or amantadine. Many other agents may be used nonspecifically for symptom control, including benzodiazepines, neuroleptics, and antiepileptic medications. In addition to motor symptoms, patients with Huntington disease or other choreic disorders often experience increasing depression, bradykinesia, cognitive impairment, aggressive behaviors, and other complications as the disease progresses. Caring for the caregiver is also a significant concern in the long-term treatment of choreic disorders.
Managing nonmotor complications
In addition to addressing chorea, it is also important to manage nonmotor complications of Huntington disease, including cognition, mood, and thought disorders. Rivastigmine was assessed for the treatment of motor symptoms, functional disability, and cognitive impairment associated with Huntington disease in an open-label study of 18 patients; 11 received rivastigmine 6 mg/day and 7 control patients did not.15 Motor and cognitive function were assessed for up to 2 years by raters who were blinded to treatment assignment. Ratings on a global motor performance scale were significantly better for patients who received rivastigmine than for control subjects. Rivastigmine treatment was also associated with trends toward improvements in functional disability and cognitive impairment, although these differences were not statistically significant.
A small open-label study examined the effects of donepezil for movement and cognitive symptoms associated with Huntington disease.16 Donepezil did not significantly improve cognitive symptoms, although the study enrolled only eight patients. All patients tolerated oral donepezil at a dose of 5 mg/day, but four patients withdrew from the study when the dose was increased to 10 mg/day. In two patients, chorea worsened and falls increased, moderate to severe diarrhea developed in three patients, and one patient reported anxiety and irritability.
Depression is another common complication of Huntington disease. The incidence of depression among patients with Huntington disease is approximately 40%, and the risk of suicide is at least eightfold greater than that among the general population.17 Treatment must be guided by clinical judgment. Selective serotonin reuptake inhibitor antidepressants have been recommended. Other options to manage depression include mirtazapine, monoamine oxidase inhibitors, or electroshock therapy. Mood-stabilizing agents (eg, carbamazepine, lamotrigine, valproate) may also be indicated in helping with impulse control. Haloperidol and second-generation antipsychotics are used for the treatment of a broad range of psychiatric conditions, many of which may overlap with Huntington disease, including schizophrenia and schizophreniform disorder, schizoaffective disorder, bipolar disorder, dementia, and disruptive behavior.18 The risk of tardive dyskinesia may be as much as fivefold lower with second-generation antipsychotics.18 Many patients with Huntington disease require treatment for aggression. A variety of approaches are available, including behavior modification, the antidepressant sertraline, buspirone, antipsychotic agents (eg, risperidone, olanzapine), propranolol, and lithium (combined with haloperidol).
Long-term care considerations
As a consequence of the diverse clinical manifestations of choreic disorders in movement, function, mood, and cognition, the treatment of Huntington disease requires a multidisciplinary approach that involves a number of different health care specialties across the long-term course of the disorder. Members of the Huntington disease treatment team may include neurologists, psychiatrists, nurses, social workers, geneticists, physical therapists, occupational therapists, speech therapists, dietitians, and other supporting groups or professional societies. The clinical manifestations of Huntington disease may evolve over time, as symptoms such as bradykinesia, dystonia, rigidity, cognitive decline, and gait instability become more significant.19 As a result, optimal management strategies for patients with Huntington disease may change significantly across the long-term course of the disease. During the early course of the disease, the typical clinical presentation is largely hyperkinesis, irritability, and distractibility. These patients will require initiation of drug therapy and linkage to sources of support. In the later stages of the disease, the presentation shifts to a more hypokinetic and apathetic profile, and patients are more likely to require drug regimen review and modification, nursing home placement, and palliative care services.19
Another important concern in Huntington disease treatment is care of the caregiver. Surveys show that the key concerns of caregivers include the expertise of the health care professionals who are treating the patient and the availability of sufficient services in the community.20 Several resources are available for Huntington disease caregivers, including local support groups, the Huntington’s Disease Society of America, Q Foundation, and the Huntington Study Group. The Lundbeck pharmaceutical company operates a patient assistance program (LundbeckShare. com) as well as an information center that can be accessed toll free at (888)457-4273. Approximately 90% of patients who request copayment assistance qualify for aid, regardless of the type of insurance they carry.
SUMMARY AND CONCLUSIONS
The approach to a patient with chorea starts with a search for specifically treatable etiologies. Autoimmune, metabolic, and vascular causes should be sought first and treated. The symptomatic treatment of all choreas is based on the model described here for Huntington disease, and includes attention to cognitive, psychiatric, and social support issues. The recommended approach is multidisciplinary, with a change in the mix of services as the disease progresses. It is also important to recognize the burden of Huntington disease on the caregiver and consider steps to make this burden more manageable.
