Neocortical morphometry in Huntington's disease: Indication of the coexistence of abnormal neurodevelopmental and neurodegenerative processes.

Huntington's disease (HD) is an inherited, autosomal dominant disorder that is characteristically thought of as a degenerative disorder. Despite cellular and molecular grounds suggesting HD could also impact normal development, there has been scarce systems-level data obtained from in vivo human studies supporting this hypothesis. Sulcus-specific morphometry analysis may help disentangle the contribution of coexisting neurodegenerative and neurodevelopmental processes, but such an approach has never been used in HD.

Association Between Motor Symptoms and Brain Metabolism in Early Huntington Disease.

Importance: Brain hypometabolism is associated with the clinical consequences of the degenerative process, but little is known about regional hypermetabolism, sometimes observed in the brain of patients with clinically manifest Huntington disease (HD). Studying the role of regional hypermetabolism is needed to better understand its interaction with the motor symptoms of the disease.

Objective: To investigate the association between brain hypometabolism and hypermetabolism with motor scores of patients with early HD.

Automatic segmentation of the striatum and globus pallidus using MIST: Multimodal Image Segmentation Tool.

Accurate segmentation of the subcortical structures is frequently required in neuroimaging studies. Most existing methods use only a T1-weighted MRI volume to segment all supported structures and usually rely on a database of training data. We propose a new method that can use multiple image modalities simultaneously and a single reference segmentation for initialisation, without the need for a manually labelled training set.

pH as a biomarker of neurodegeneration in Huntington's disease: a translational rodent-human MRS study.

Early diagnosis and follow-up of neurodegenerative diseases are often hampered by the lack of reliable biomarkers. Neuroimaging techniques like magnetic resonance spectroscopy (MRS) offer promising tools to detect biochemical alterations at early stages of degeneration. Intracellular pH, which can be measured noninvasively by (31)P-MRS, has shown variations in several brain diseases.

The neural substrates of script knowledge deficits as revealed by a PET study in Huntington's disease.

Introduction: Previous neuropsychological investigations have suggested that both the prefrontal cortex and the basal ganglia are involved in the management of script event knowledge required in planning behavior.

Methods: This study was designated to map, the correlations between resting-state brain glucose utilization as measured by FDG-PET (positron emission tomography) and scores obtained by means of a series of script generation and script sorting tasks in 8 patients with early Huntington's disease.

Results: These patients exhibited a selectively greater impairment for the organizational aspects of scripts compared to the semantic aspects of scripts.

Comparison of eight methods for the estimation of the image-derived input function in dynamic [(18)F]-FDG PET human brain studies.

The aim of this study was to compare eight methods for the estimation of the image-derived input function (IDIF) in [(18)F]-FDG positron emission tomography (PET) dynamic brain studies. The methods were tested on two digital phantoms and on four healthy volunteers. Image-derived input functions obtained with each method were compared with the reference input functions, that is, the activity in the carotid labels of the phantoms and arterial blood samples for the volunteers, in terms of visual inspection, areas under the curve, cerebral metabolic rates of glucose (CMRglc), and individual rate constants.

In vivo evidence for the selective subcortical degeneration in Huntington's disease.

Although Huntington's disease is largely considered to be a subcortical disease, there is no clear consensus on whether all deep grey matter loss is a direct downstream consequence of the massive degeneration of the medium-size spiny neurons in the striatum. Our aim was to characterise in vivo such preferential degeneration by analysing various distinct diffusion imaging measures including mean diffusivity, anisotropy, fibre orientation (using the information of the principal diffusion direction) and white matter tractography. All results converged to demonstrate the selective degeneration of connections in subcortical grey and white matter, degeneration which was likely to originate with the death of the striatal medium-size spiny neurons.

Comparison of 3 methods of automated internal carotid segmentation in human brain PET studies: application to the estimation of arterial input function.

Unlabelled: Quantitative brain (18)F-FDG PET studies often require the plasma time-activity curve (input function) for estimation of the cerebral metabolic rate of glucose (CMRglc). The gold standard for input function measurement is arterial blood sampling, which is invasive and time-consuming. Alternatively, input function can be estimated from dynamic images.

Language processing within the striatum: evidence from a PET correlation study in Huntington's disease.

The role of sub-cortical structures in language processing, and more specifically of the striatum, remains controversial. In line with psycholinguistic models stating that language processing implies both the recovery of lexical information and the application of combinatorial rules, the striatum has been claimed to be involved either in the former component or in the latter. The present study reconciles these conflicting views by showing the striatum's involvement in both language processes, depending on distinct striatal sub-regions.

Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington's disease.

Background: The brain is deemed "immunologically privileged" due to sparse professional antigen-presenting cells and lymphatic drainage, and to the blood-brain barrier. Although the actual extent of this privilege is controversial, there is general consensus about the limited need in intracerebral neural grafts for immunosuppressive regimens comparable to those used in other cases of allotransplantation. This has led over the past fifteen years to the use of either short-term or even no immunosuppression in most clinical trials with foetal neural transplant in patients with Parkinson's and Huntington's disease.

Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study.

Background: Although we have shown in three out of five patients with Huntington's disease that motor and cognitive improvements 2 years after intracerebral fetal neural grafts are correlated with recovery of brain metabolic activity in grafted striatal areas and connected regions of the cerebral cortex, neural grafts are not known to have protective effects on the host brain per se. We undertook long-term follow-up of previously reported patients with the disease to ascertain the nature and extent of any secondary decline after grafting.

Methods: Five patients with Huntington's disease from our pilot study were assessed annually with the unified Huntington's disease rating scale, neuropsychological tests, and MRI, for up to 6 years after neural grafting.

Subthalamic nucleus stimulation reduces abnormal motor cortical overactivity in Parkinson disease.

Background: Based on the basal ganglia model, it has been hypothesized that the efficacy of high-frequency stimulation of the subthalamic nucleus (STN) against parkinsonian symptoms relies on the activation of cortical premotor regions. In previous positron emission tomography activation studies, STN high-frequency stimulation was associated with selective activation of midline premotor areas during hand movements but mainly reduced the regional cerebral blood flow in movement-related areas, peculiarly at rest.

Objective: To investigate with positron emission tomography the role of regional cerebral blood flow reduction in the clinical improvement provided by STN high-frequency stimulation.

Striatal neural grafting improves cortical metabolism in Huntington's disease patients.

Huntington's disease is a hereditary disease in which degeneration of neurons in the striatum leads to motor and cognitive deficits. Foetal striatal allografts reverse these deficits in phenotypic models of Huntington's disease developed in primates. A recent open-label pilot study has shown some clinical improvement or stabilization in three out of five Huntington's disease patients who received bilateral striatal grafts of foetal neurons.

Association of chorea and motor neuron disease.

Amyotrophic lateral sclerosis (ALS) is classically characterized by the presence of symptoms or signs of upper and lower motor neuron impairment and sparing of other neuronal systems.1 We report on a patient who was primarily diagnosed as typical ALS and developed chorea 10 years after the onset of motor neuron signs.