There are currently no effective pharmacological agents available to stop or prevent the progression of Huntington’s disease (HD), a rare hereditary neurodegenerative disorder. In addition to psychiatric symptoms and cognitive impairments, HD causes progressive motor disturbances, in particular choreiform movements, which are characterized by unwanted contractions of the facial muscles, trunk and extremities. Management of choreiform movements is usually advised if chorea interferes with daily functioning, causes social isolation, gait instability, falls, or physical injury. Although drugs to reduce chorea are available, only few randomized controlled studies have assessed the efficacy of these drugs, resulting in a high variety of prescribed drugs in clinical practice. The current pharmacological treatment options to reduce chorea in HD are outlined in this review, including the latest results on deutetrabenazine, a newly developed pharmacological agent similar to tetrabenazine, but with suggested less peak dose side effects. A review of the existing literature was conducted using the PubMed, Cochrane and Medline databases. In conclusion, mainly tetrabenazine, tiapride (in European countries), olanzapine, and risperidone are the preferred first choice drugs to reduce chorea among HD experts. In the existing literature, these drugs also show a beneficial effect on motor symptom severity and improvement of psychiatric symptoms. Generally, it is recommended to start with a low dose and increase the dose with close monitoring of any adverse effects. New interesting agents, such as deutetrabenazine and pridopidine, are currently under development and more randomized controlled trials are warranted to assess the efficacy on chorea severity in HD.
BackgroundProgressive subcortical changes are known to occur in Huntington's disease (HD), a hereditary neurodegenerative disorder. Less is known about the occurrence and cohesion of whole brain grey matter changes in HD.ObjectivesWe aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments.MethodsStructural magnetic resonance imaging data of premanifest HD (n = 30), HD patients (n = 30) and controls (n = 30) was used to identify ten structural covariance networks based on a novel technique using the co-variation of grey matter with independent component analysis in FSL. Group differences were studied controlling for age and gender. To explore whether our approach is effective in examining grey matter changes, regional voxel-based analysis was additionally performed.ResultsPremanifest HD and HD patients showed decreased network integrity in two networks compared to controls. One network included the caudate nucleus, precuneous and anterior cingulate cortex (in HD p < 0.001, in pre-HD p = 0.003). One other network contained the hippocampus, premotor, sensorimotor, and insular cortices (in HD p < 0.001, in pre-HD p = 0.023). Additionally, in HD patients only, decreased network integrity was observed in a network including the lingual gyrus, intracalcarine, cuneal, and lateral occipital cortices (p = 0.032). Changes in network integrity were significantly associated with scores of motor and neuropsychological assessments. In premanifest HD, voxel-based analyses showed pronounced volume loss in the basal ganglia, but less prominent in cortical regions.ConclusionOur results suggest that structural covariance might be a sensitive approach to reveal early grey matter changes, especially for premanifest HD.
Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder characterized by motor disturbances, psychiatric disturbances, and cognitive impairment. Visual cognitive deficits and atrophy of the posterior cerebral cortex are additionally present in early disease stages. This study aimed to assess the extent of structural and functional brain alterations of the visual cortex in HD gene carriers using different neuroimaging modalities. Structural and functional magnetic resonance imaging data were acquired from 18 healthy controls, 21 premanifest, and 20 manifest HD gene carriers. Voxel-based morphometry (VBM) analysis and cortical thickness measurements were performed to assess structural changes in the visual cortex. Brain function was measured by assessing neuronal connectivity changes in response to visual stimulation and at rest in visual resting-state networks. Multiple linear regression analyses were performed to examine the relationship between visual cognitive function and structural imaging measures. Compared to controls, pronounced atrophy and decreased neuronal function at rest were present in associative visual cortices in manifest HD. The primary visual cortex did not show group differences in cortical thickness and in vascular activity after visual stimulation. Thinning of the associative visual cortex was related to worse visual perceptual function. Premanifest HD gene carriers did not show any differences in brain structure or function compared to controls. This study improves the knowledge on posterior brain changes in HD, as our findings suggest that the primary visual cortex remains preserved, both structurally and functionally, while atrophy of associative visual cortices is present in early HD and linked to clinical visual deficits.
BackgroundHuntington's disease (HD) is characterized by motor and behavioral symptoms, and cognitive decline. HD gene carriers and their caregivers report the behavioral and cognitive symptoms as the most burdensome. Apathy is the most common behavioral symptom of HD and is related to clinical measures of disease progression, like functional capacity. However, it is unknown whether apathy is directly related to the neurodegenerative processes in HD.ObjectiveThe aim is to investigate whether an association between atrophy of subcortical structures and apathy is present in HD, at baseline and after 2 years follow-up.MethodVolumes of 7 subcortical structures were measured using structural T1 MRI in 171 HD gene carriers of the TRACK-HD study and apathy was assessed with the Problem Behaviors Assessment-Short, at baseline and follow-up visit. At baseline, logistic regression was used to evaluate whether volumes of subcortical brain structures were associated with the presence of apathy. Linear regression was used to assess whether subcortical atrophy was associated with the degree of apathy at baseline and with an increase in severity of apathy over time.ResultsAt baseline, smaller volume of the thalamus showed a higher probability of the presence of apathy in HD gene carriers, but none of the subcortical structures was associated with the degree of apathy. Over time, no association between atrophy of any subcortical structures and change in degree of apathy was found.ConclusionThe presence of apathy is associated with atrophy of the thalamus in HD, suggesting that apathy has an underlying neural cause and might explain the high incidence of apathy in HD. However, no association was found between atrophy of these subcortical structures and increase in severity of apathy over a 2-year time period.
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