Structure and function of the cerebral cortex in Huntington's disease

Huntington’s disease (HD) is a progressive autosomal dominant inherited neurodegenerative disorder.The primary aim of this thesis is to examine alterations in the cerebral cortex in HD gene carriers. Different image modalities and approaches will be used to extent the knowledge on both structural and functional cortical brain changes in early disease. Although striatal atrophy is more extensively present in HD, changes in the cerebral cortex can also be detected in the pre-symptomatic stage. Different methodological approaches used in our studies all showed a consistent pattern of cortical atrophy making volumetric MRI a reliable and effective tool to assess early in-vivo cortical brain changes, even in a rare neurodegenerative disorder such as HD. The influence of cortical changes on other clinical signs that occur in HD should not be overlooked. Our results demonstrate that volume loss and thinning of the cerebral cortex, especially the posterior brain regions, is detectable in early stages and contributes to the presence of specific motor signs and cognitive impairments. We believe that intervention trials could benefit from using cortical volumes as outcome measures, instead of using striatal volumes alone.Chipsoft; Verengiging van Huntington; Stichting Alkemade-Keuls; Afdeling Neurologie LUMCLUMC / GeneeskundeLUMC / Geneeskunde Repositoriu

The visual cortex and visual cognition in Huntington's disease: An overview of current literature

Neuro Imaging Researc

Structure and function of the cerebral cortex in Huntington's disease

Huntington’s disease (HD) is a progressive autosomal dominant inherited neurodegenerative disorder.The primary aim of this thesis is to examine alterations in the cerebral cortex in HD gene carriers. Different image modalities and approaches will be used to extent the knowledge on both structural and functional cortical brain changes in early disease. Although striatal atrophy is more extensively present in HD, changes in the cerebral cortex can also be detected in the pre-symptomatic stage. Different methodological approaches used in our studies all showed a consistent pattern of cortical atrophy making volumetric MRI a reliable and effective tool to assess early in-vivo cortical brain changes, even in a rare neurodegenerative disorder such as HD. The influence of cortical changes on other clinical signs that occur in HD should not be overlooked. Our results demonstrate that volume loss and thinning of the cerebral cortex, especially the posterior brain regions, is detectable in early stages and contributes to the presence of specific motor signs and cognitive impairments. We believe that intervention trials could benefit from using cortical volumes as outcome measures, instead of using striatal volumes alone.</p

Current Pharmacological Approaches to Reduce Chorea in Huntington's Disease

Neurological Motor Disorder

Structural and functional changes of the visual cortex in early Huntington's disease

Neuro Imaging Researc

Visual Object Perception in Premanifest and Early Manifest Huntington's Disease

Objective: In Huntington's disease (HD), a hereditary neurodegenerative disorder, cognitive impairment in early disease stages mainly involves executive dysfunction. However, visual cognitive deficits have additionally been reported and are of clinical relevance given their influence on daily life and overall cognitive performance. This study aimed to assess visual perceptual skills in HD gene carriers.Methods: Subtasks of the Visual Object and Space Perception battery and Groningen Intelligence Test were administered in 62 participants (18 healthy controls, 22 participants with a genetic confirmation of HD without symptoms, i.e., premanifest HD, and 22 participants with a genetic confirmation of HD with symptoms, i.e., manifest HD). Group differences in task performance were measured using analysis of covariance with and without correction for age. Receiver Operating Characteristics (ROC) analysis was performed to examine which task best discriminated between groups and cut-off scores were provided.Results: Manifest HD performed significantly worse compared to both controls and premanifest HD on all visual perceptional tasks. Premanifest HD did not differ in task performance from controls. Besides the Shape Detection, all tasks were robust in discriminating between groups. The Animal Silhouettes test was most accurate in discriminating manifest HD from premanifest HD (AUC = 0.90, SE = 0.048, p < .001).Conclusion: Visual perceptual deficits are present in early manifest HD, especially an impaired recognition of animals and objects from sketched silhouettes, and not in premanifest HD. This suggests that decline in visual processing only occurs in clinical disease stages. The visual cognitive battery, especially the Silhouettes tasks used in this study is sensitive in discriminating manifest HD from premanifest HD and controls.Neurological Motor Disorder

Three dimensional evaluation of facial asymmetry after mandibular reconstruction: validation of a new method using stereophotogrammetry

Item does not contain fulltextThe scientific literature is sparse on reports that evaluate facial asymmetry after mandibular reconstructive surgery objectively. The aim of this study is to introduce and validate a new method, using three dimensional (3D) stereophotogrammetry, that quantifies soft-tissue facial asymmetry in patients who have undergone mandibular reconstruction. To validate the new method, two observers applied the method on 3D photographs of five patients and five controls. An inter-observer difference of 0.04 mm (-0.08 to 0.17) was found with a measurement error of 0.13 mm. 15 3D photographs of the mandibular reconstructed patients were compared with 24 3D photographs of healthy controls. A significant difference (1.19 mm) in asymmetry was found between patients and controls. It is concluded that this new measuring method is a valid, fast and clinically applicable technique to quantify soft-tissue facial asymmetry. It is concluded that facial symmetry in patients is not restored to the level of the control group with the mandibular reconstruction method applied

Grey matter volume loss is associated with specific clinical motor signs in Huntington's disease

Neurological Motor Disorder

Apathy and atrophy of subcortical brain structures in Huntington's disease: A two-year follow-up study

Background: Huntington'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. Objective: The 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. Method: Volumes 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. Results: At 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. Conclusion: The 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. Keywords: Apathy, Huntington's disease, Subcortical structures, Thalamu