Effects of multidisciplinary therapy on physical function in Huntington's disease

Huntington's disease is a genetic disorder that causes motor dysfunction, personality changes, dementia, and premature death. There is currently no effective therapy. Several transgenic models of Huntington's disease are available, the most widely used of which is the R6/2 mouse, because of its rapid disease progression. Environmental enrichment alters gene expression in the normal mouse brain, and modulates the course of several neurological disorders. Environmentally enriched mice may actually mimic human disease more accurately. We found that even limited environmental enrichment slows decline in RotaRod performance in R6/2 mice, despite rapid disease progression, whereas in normal littermates, maximal enrichment was required to induce a marked improvement in behavioral tests. Enrichment also delayed the loss of peristriatal cerebral volume in R6/2 brains. These results could provide the basis for a rational approach to ameliorate the effects of Huntington's disease.

To determine whether motor, behavioral, or psychiatric symptoms in Huntington disease (HD) predict skilled nursing facility (SNF) placement. Subjects were participants in the Huntington Study Group's Unified Huntington Disease Rating Scale Database (Rochester, NY) between January 1994 and September 1999. Specific motor, psychiatric, and behavioral variables in subjects residing at home and in SNF were analyzed using chi2 and Student's t-tests. For a subset of subjects for whom longitudinal data existed, a Cox proportional hazards model controlling for age, sex, and disease duration was used. Among 4,809 subjects enrolled, 3,070 had clinically definite HD. Of these, 228 (7.4%) resided in SNF. The SNF residents' average age was 52 years, average disease duration was 8.6 years, and they were predominantly women (63%). The SNF residents had worse motor function (chorea, bradykinesia, gait abnormality, and imbalance, p < 0.0001); were more likely to have obsessions, compulsions, delusions, and auditory hallucinations; and had more aggressive, disruptive (p < 0.0001), and irritable behaviors (p = 0.0012). For 1,559 subjects, longitudinal data existed (average length of follow-up, 1.9 years), and 87 (5%) moved from home to SNF. In the Cox model, bradykinesia (HR 1.965, 95% CI 1.083 to 3.564), impaired gait (HR 3.004, 95% CI 1.353 to 6.668), and impaired tandem walking (HR 2.546, 95% CI 1.460 to 4.439) were predictive of SNF placement. Institutionalized patients with HD are more motorically, psychiatrically, and behaviorally impaired than their counterparts living at home. However, motor variables alone predicted institutionalization. Treatment strategies that delay the progression of motor dysfunction in HD may postpone the need for institutionalization.