Assessment of complex movements reflects dysfunction in Huntington?s disease

Abstract

Results of various complex instrumental tools, rating scales, caudate atrophy and CAG repeat length may reflect the severity of Huntington's disease (HD). A simple assessment task for dysfunction due to disease is the standardized, computer based performance of peg insertion. The objectives of our study were to compare scored HD symptoms, computed bicaudate diameter ratio (BDR), age related genetic disease load (CAG index = [CAG-35.5 x age]) and peg insertion scores between asymptomatic 34 HD gene carriers, 89 previously untreated HD patients with psychiatric or motor symptoms, or both, and 51 treated HD patients. We measured the period of the total time taken to insert 25 pegs from a rack into a series of appropriate holes, calculated the CAG index, estimated the bicaudate diameter ratio (BDR) of a current brain CT and scored the HD patients under blind conditions. Times for the peg insertion task significantly differed between HD patients and controls, but not between HD gene carriers and controls. BDR and CAG index reflected the increase of symptoms in HD. Peg insertion results and scored severity of HD, BDR and CAG index significantly correlated with each other. Peg insertion scores are not specific diagnostic markers for HD, but they reflect clinical symptoms of neurodegeneration. The performance of peg insertion involves visuospatial cognition, self-elaboration of internal strategies, sorting and planning of movement. Therefore peg insertion particularly reflects executive dysfunction in early HD and additionally motor impairment in advanced HD.

Rivastigmine in the treatment of patients with Alzheimer's disease

“…A further trial that investigated the impact of transdermal rivastigmine administration on motor performance with an altered standardized peg insertion paradigm showed that patients with predominant cholinergic neurodegeneration need longer for performance of the peg insertion paradigm in comparison with controls. Thus this study confirms a deterioration in carrying out of complex motion series in neurodegenerative processes, because this was also shown in disorders with preponderant functional basal ganglia disturbances, ie, Huntington’s disease or PD (Müller et al 2000; Saft et al 2003, 2004). This trial also confirmed that assessment of co-ordinated movements with the non-dominant hand better reflects disturbances of fine motor behavior during neurodegeneration probably due to regular training and use (Müller et al 2000, 2003b; Pal et al 2001; van Vugt et al 2001; Saft et al 2003, 2004).…”

“…Thus this study confirms a deterioration in carrying out of complex motion series in neurodegenerative processes, because this was also shown in disorders with preponderant functional basal ganglia disturbances, ie, Huntington’s disease or PD (Müller et al 2000; Saft et al 2003, 2004). This trial also confirmed that assessment of co-ordinated movements with the non-dominant hand better reflects disturbances of fine motor behavior during neurodegeneration probably due to regular training and use (Müller et al 2000, 2003b; Pal et al 2001; van Vugt et al 2001; Saft et al 2003, 2004). An improved brain plasticity of the dominant brain hemisphere with secondary better compensation of motor deficits may additionally be responsible for the inferior sensitivity of the applied instrumental paradigm to reflect motor disturbances of the upper limb during a neurodegenerative process (Van Hilten et al 1993; Müller et al 2000, 2003b; van Vugt et al 2001; Ioffe 2004; Saft et al 2004).…”

Functional connectivity of the prefrontal cortex in Huntington's disease

“…22 In this study, the CAG index ranged from 29.5 to 666.5 (mean (SD) 363 (136)). The controls had no history of a neurological or psychiatric disorder.…”

“…Hence, the patients with Huntington's disease showed significantly greater activation than controls bilaterally in the caudal anterior cingulate gyrus, right dorsal premotor cortex, right inferior frontal gyrus, left middle frontal gyrus, and left superior parietal lobule. As our aim was to examine prefrontal connectivity, we selected peak voxels from these activation results within the anterior cingulate (left/right: coordinates (mm) ¡10, 38,22) and lateral prefrontal regions on the border of inferior and middle frontal gyri (left/right: coordinates (mm) ¡38, 44, 16) to model prefrontal functional connectivity (fig 3). ROIs were defined as 6 mm diameter spheres centred on the selected peak voxels.…”

Entacapone improves complex movement performance in patients with Parkinson’s disease

“…Huntington's disease or PD. 1,9 This instrumental tool was sensitive enough to reflect the antiparkinsonian efficacy of a single administration of levodopa/decarboxylase inhibitor formulation and or of daily amantadine sulphate infusions during an interval of three days in PD patients. 2,4,10 In these trials, we avoided the comparison against placebo intake, which may also stimulate the nigrostriatal system due to release of dopamine and thus may confound the rating and motor test outcomes.…”