Bradykinesia in early Huntington's disease.

BACKGROUND: Huntington's disease (HD) is generally considered a hyperkinetic disorder, although hypokinetic features are part of the motor syndrome. Moreover, the striatum is considered to play a key role in initiating and executing motor programs and achieving optimal scheduling in response generation. Controversial results regarding the association between clinical features and markers of progression of the disease might be the result of inadequate restriction of clinical signs to the choreatic syndrome. OBJECTIVE: To determine the relationship of neurologic motor and cognitive indices in patients with HD with intrinsic neuronal loss in the striatum, as measured using raclopride C11 and PET. PATIENTS AND METHODS: A cross-sectional study was performed on 11 patients with mild HD (stages 0-2). Motor (Unified Huntington's Disease Rating Scale [UHDRS], saccadic and tapping speed) and cognitive (verbal fluency, Trail Making Test, Stroop Test, Symbol Digit Modalities Test, Conditioned Associative Learning Test, and silhouette identification and object decision of the Visual Object and Space Perception battery) scores were correlated with raclopride C11 binding. RESULTS: Bradykinesia (a summation of five items of the UHDRS motor scale) was the best predictor for stage, that is, functional capacity, and showed a highly significant relationship with putaminous D2 binding (r = -0.94) and with CAG expansion length x years of age (r = 0.96). The exclusion of two patients with a rigid-akinetic HD variant did not alter these coefficients. Chorea was less well correlated than bradykinesia with D2 binding in all striatal regions. Performance on different cognitive tests, especially in timed tasks, was highly correlated with raclopride C11 binding in caudate nucleus and ventral striatum. CONCLUSION: Loss of D2 binding in the striatum is highly correlated with the deficit in fast motor and cognitive processing in patients with early Huntington's Disease. Thus, impairment of rapid execution of adequate responses to environmental changes seems to be a common manifestation of striatal disorders.

Clinical correlation of striatal 1H MRS changes in Huntington's disease.

OBJECTIVE: To study the clinical significance of metabolic alterations as measured in vivo with proton MRS in the striatum of patients with Huntington's disease (HD). METHODS: Localized, single-voxel MRS was performed on the basal ganglia of 10 HD patients (4 presymptomatic gene carriers and 6 akinetic patients) and 5 age-matched healthy individuals. Metabolite quantification was performed by referring the areas of the respective spectral peaks to that of water in the analyzed voxel. The spectroscopic findings were correlated with motor and cognitive performance in several specific tests and with the length of the CAG repeat expansion normalized for age. RESULTS: N-acetylaspartate (NAA) and creatine were reduced markedly in both groups of patients, particularly in the advanced group (approximately 60%), but the decrease was also significant in presymptomatic patients (approximately 30%) whose motor and cognitive performances were within the normal range. Both metabolites correlated highly with the motor score of the Unified Huntington's Disease Rating Scale and with computed measurements of saccadic and tapping speed. Creatine reduction was also well correlated with performance in cognitive timed tasks and with the length of CAG expansion (r = -0.81). CONCLUSION: The creatine signal appears to be an interesting marker for progression in HD and could be useful in assessing therapeutic outcome, particularly during the initial stages when most clinical indices are still within the normal range.

[Cognitive assessment of asymptomatic Huntington's disease carriers]. / Estudio cognitivo de portadores asintomáticos de la enfermedad de Huntington.

The recent availability of a genetic analysis for the diagnosis of Huntington's disease (HD) allows now for a careful study of presymptomatic stages of the disease. The aim of this study was to see if subtle cognitive deficits could be elicited on formal neuropsychological testing in asymptomatic HD carriers. Thirty-six individuals at risk for HD, applying for genetic assessment, were studied with a cognitive protocol covering attention, memory, visuospatial and prefrontal functions. Gene IT15 analysis revealed an abnormal expansion of (CAG) trinucleotide repeats in 18 subjects, being normal in the remaining 18. The comparison of the neuropsychological performance between both groups did not show significant differences in any of the cognitive domains. These data support that there is no premorbid cognitive impairment in HD, at least recognizable with the current measures of assessment.

[Relation between frontal lobe blood flow and cognitive performance in Huntington's disease]. / Relación entre flujo sanguíneo cerebral frontal y rendimiento cognitivo en la enfermedad de Huntington.

The aim of this study was to trace the possible relation between degree of cognitive impairment in Huntington's disease (HD) and cortical cerebral blood flow. We studied 18 patients with genetically confirmed HD, evaluating clinical signs and performance on neuropsychological tests. SPECT with 99mTc-HMPAO was used to quantify regional cerebral blood flow (rCBF) in 8 regions in each hemisphere. We found no correlation between clinical or cognitive variables and rCBF in temporal, parietal or occipital areas. Cognitive performance on several tasks correlated significantly with rCBF (p < 0.05 or p < 0.01) in numerous frontal areas with the exception of orbital gyri. These data suggest that frontal lobe dysfunction is implicated in the pathogenesis of cognitive impairment in HD, and that such impairment can be explained by the involvement of frontal-subcortical loops.