Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine

Dystonia and dopamine: From phenomenology to pathophysiology

A line of evidence suggests that the pathophysiology of dystonia involves the striatum, whose activity is modulated among other neurotransmitters, by the dopaminergic system. However, the link between dystonia and dopamine appears complex and remains unclear. Here, we propose a physiological approach to investigate the clinical and experimental data supporting a role of the dopaminergic system in the pathophysiology of dystonic syndromes. Because dystonia is a disorder of motor routines, we first focus on the role of dopamine and striatum in procedural learning. Second, we consider the phenomenology of dystonia from every angle in order to search for features giving food for thought regarding the pathophysiology of the disorder. Then, for each dystonic phenotype, we review, when available, the experimental and imaging data supporting a connection with the dopaminergic system. Finally, we propose a putative model in which the different phenotypes could be explained by changes in the balance between the direct and indirect striato-pallidal pathways, a process critically controlled by the level of dopamine within the striatum. Search strategy and selection criteria References for this article were identified through searches in PubMed with the search terms « dystonia », « dopamine”, « striatum », « basal ganglia », « imaging data », « animal model », « procedural learning », « pathophysiology », and « plasticity » from 1998 until 2018. Articles were also identified through searches of the authors' own files. Only selected papers published in English were reviewed. The final reference list was generated on the basis of originality and relevance to the broad scope of this review

Erratum: Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia (Brain (2021) 144:3 (909-923) DOI: 10.1093/brain/awaa465)

The publisher apologizes for an error in the author details. This has been corrected

Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia

Early-onset torsion dystonia (TOR1A/DYT1) is a devastating hereditary motor disorder whose pathophysiology remains unclear. Studies in transgenic mice suggested abnormal cholinergic transmission in the putamen, but this has not yet been demonstrated in humans. The role of the cerebellum in the pathophysiology of the disease has also been highlighted but the involvement of the intrinsic cerebellar cholinergic system is unknown. In this study, cholinergic neurons were imaged using PET with 18F-fluoroethoxybenzovesamicol, a radioligand of the vesicular acetylcholine transporter (VAChT). Here, we found an age-related decrease in VAChT expression in the posterior putamen and caudate nucleus of DYT1 patients versus matched controls, with low expression in young but not in older patients. In the cerebellar vermis, VAChT expression was also significantly decreased in patients versus controls, but independently of age. Functional connectivity within the motor network studied in MRI and the interregional correlation of VAChT expression studied in PET were also altered in patients. These results show that the cholinergic system is disrupted in the brain of DYT1 patients and is modulated over time through plasticity or compensatory mechanisms

Dementia associated with disorders of the basal ganglia

Dementia is now the leading cause of death in the United Kingdom, accounting for over 12% of all deaths and is the fifth most common cause of death world-wide. As treatments for heart disease and cancers improve and the population ages, the number of sufferers will only increase, with the chance of developing dementia doubling every 5 years after the age of 65. Finding an effective treatment is ever more critical to avert this pandemic health (and economic) crisis. To date, most dementia-related research has focused on cortex and hippocampus, however, with dementia becoming more fully recognized as aspects of diseases historically categorized as motor disorders (e.g. Parkinson’s and Huntington’s diseases), the role of the basal ganglia in dementia is coming to the fore. Conversely, it is highly likely that neuronal pathways in these structures traditionally considered as spared in Alzheimer’s disease are also affected, particularly in later stages of the disease. In this review we examine some of the limited evidence linking the basal ganglia to dementia

Brain imaging in RBD.

Neuroimaging studies can provide in vivo insights to the early structural and functional brain changes in patients with idiopathic RBD (iRBD) and may help give a prognosis of disease course. This chapter summarizes the major findings of neuroimaging studies in iRBD, a specific prodromal stage of Parkinson’s disease (PD) and other α-synucleinopathies. Molecular imaging techniques, magnetic resonance imaging (MRI), and transcranial sonography (TCS) are all discussed