Journal of Huntington's Disease - Volume 2, issue 4

Authors: Dorsey, E. Ray | Brocht, Alicia F.D. | Nichols, Paige E. | Darwin, Kristin C. | Anderson, Karen E. | Beck, Christopher A. | Singh, Sonal | Biglan, Kevin M. | Shoulson, Ira

Article Type: Research Article

Abstract: Background: Tetrabenazine, a treatment for chorea in Huntington disease, carries a boxed warning due to safety, especially related to suicidality. Objective: To compare the frequency of depressed mood and suicidality among a closely monitored cohort of individuals with Huntington disease who were exposed and not exposed to tetrabenazine. Methods: A longitudinal prospective study involving 1360 individuals with HD evaluated at 48 research centers in Australia, Canada, and the United States was examined for frequency of depressed mood that triggered a risk assessment, suicidal thoughts, suicide attempts, and completed suicide among individuals with prior, new, and no exposure to tetrabenazine.. Seventy-seven …individuals were on tetrabenazine at study enrollment (prior exposure), 64 individuals were exposed to tetrabenazine during the study's course (new exposure), and 1219 individuals had no exposure to tetrabenazine. Results: The hazard ratio for depressed mood among those with prior exposure to tetrabenazine compared to no exposure was 0.9 (95% CI, 0.5–1.6) and for those with new exposure compared to no exposure was 1.2 (95% CI, 0.8–1.9). One individual (1.3%) with prior exposure, one individual (1.6%) with new exposure, and 35 individuals (2.9%) with no exposure to tetrabenazine reported suicidal thoughts. The hazard ratio for suicidal ideation among those with prior exposure to tetrabenazine compared to no exposure was 0.5 (95% CI, 0.1–3.8) and for those with new exposure to tetrabenazine compared to no exposure was 0.6 (95% CI, 0.1–4.4). Among individuals with prior or new exposure to tetrabenazine, no suicide attempts or suicides occurred. Among those with no exposure to tetrabenazine 17 suicide attempts (1.4%) and four suicides (0.3%) occurred. Conclusions: In a large observational study with close clinical supervision, tetrabenazine treatment was not associated with an increased risk of depressed mood, suicidal ideation, suicide attempts, or suicide. Show more

Keywords: Depression, Huntington disease, suicide, tetrabenazine, U.S. Food and Drug Administration

DOI: 10.3233/JHD-130071

Citation: Journal of Huntington's Disease, vol. 2, no. 4, pp. 509-515, 2013

Authors: Crawford, Helen E. | Hobbs, Nicola Z. | Keogh, Ruth | Langbehn, Douglas R. | Frost, Chris | Johnson, Hans | Landwehrmeyer, Bernhard | Reilmann, Ralf | Craufurd, David | Stout, Julie C. | Durr, Alexandra | Leavitt, Blair R. | Roos, Raymund A.C. | Tabrizi, Sarah J. | Scahill, Rachael I. | the TRACK-HD Investigators

Article Type: Research Article

Abstract: Background: Volumetric MRI studies have highlighted the pronounced loss of white matter in premanifest and early Huntington's Disease (HD). The current study focussed on the corpus callosum (CC) since it provides interhemispheric connections to vulnerable cortical areas. Objectives: To investigate cross-sectional and longitudinal group differences in CC volume and hypothesis-driven associations with three cognitive tasks. Methods: Baseline and 24-month 3T MRI were analysed from 106 premanifest (PreHD), (59 preHD-A ≥10.8 and 47 preHD-B <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2 (HD2)) and 101 control subjects from the TRACK-HD study, using a …semi-automated technique for CC delineation. Between-group differences in volume and 24-month atrophy rates, and correlations with cognitive performance were investigated using regression models, adjusting for potential confounders. Results: PreHD-B, HD1 and HD2 had statistically significantly smaller baseline CC volumes (p < 0.001) and all groups had elevated 24-month atrophy rates compared with controls (p < 0.001). Smaller baseline CC volume was associated with impaired performance in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non-statistically significant relationships with Stroop Word Reading were shown in both gene-positive groups. There was no evidence of an association with the Trail Making B task. Conclusions: We found reduced CC volume and elevated 24-month atrophy rates, even in individuals far from disease onset. Structural degeneration of interhemispheric connections may contribute to cognitive deficits, such as performance in the Circle Tracing Indirect task in HD. Examination of different image acquisitions may provide more specific information about underlying CC degeneration. Show more

Keywords: Huntington's disease, MRI, corpus callosum, atrophy

DOI: 10.3233/JHD-130077

Citation: Journal of Huntington's Disease, vol. 2, no. 4, pp. 517-526, 2013

Article Type: Other

DOI: 10.3233/JHD-139010

Citation: Journal of Huntington's Disease, vol. 2, no. 4, pp. 527-527, 2013

Article Type: Other

Citation: Journal of Huntington's Disease, vol. 2, no. 4, pp. 529-533, 2013