Corticobasal syndrome: neuroimaging and neurophysiological advances

Corticobasal degeneration (CBD) is a neurodegenerative condition characterized by 4R-tau protein deposition in several brain regions that clinically manifests itself as a heterogeneous atypical parkinsonism typically expressing in the adulthood. The prototypical clinical phenotype of CBD is corticobasal syndrome (CBS). Important insights into the pathophysiological mechanisms underlying motor and higher cortical symptoms in CBS have been gained by using advanced neuroimaging and neurophysiological techniques. Structural and functional neuroimaging studies often showed asymmetric cortical and subcortical abnormalities, mainly involving perirolandic and parietal regions and basal ganglia structures. Neurophysiological investigations including electroencephalography and somatosensory evoked potentials provided useful information on the origin of myoclonus and on cortical sensory loss. Transcranial magnetic stimulation demonstrated heterogeneous and asymmetric changes in the excitability and plasticity of primary motor cortex and abnormal hemispheric connectivity. Neuroimaging and neurophysiological abnormalities in multiple brain areas reflect the asymmetric neurodegeneration, leading to the asymmetric motor and higher cortical symptoms in CBS. This article is protected by copyright. All rights reserved

Reproducible metabolic topographies associated with multiple system atrophy: Network and regional analyses in Chinese and American patient cohorts

© 2020 The Authors Purpose: Multiple system atrophy (MSA) is an atypical parkinsonian syndrome and often difficult to discriminate clinically from progressive supranuclear palsy (PSP) and Parkinson\u27s disease (PD) in early stages. Although a characteristic metabolic brain network has been reported for MSA, it is unknown whether this network can provide a clinically useful biomarker in different centers. This study was aimed to identify and cross-validate MSA-related brain network and assess its ability for differential diagnosis and clinical correlations in Chinese and American patient cohorts. Methods: We included 18F-FDG PET scans retrospectively from 128 clinically diagnosed parkinsonian patients (34 MSA, 34 PSP and 60 PD) and 40 normal subjects in China and in the USA. Using PET images from 20 moderate-stage MSA patients of parkinsonian subtype and 20 normal subjects in both centers, we reproduced MSA-related pattern (MSAPRP) of spatial covariance and estimated its reliability. MSAPRP scores were evaluated in assessing differential diagnosis among moderate- and early-stage MSA, PSP or PD patients and clinical correlations with disease severity. Regional metabolic differences were detected using statistical parameter mapping analysis. MSA-related network and regional topographies of metabolic abnormality were cross-validated between the Chinese and American cohorts. Results: We generated a highly reliable MSAPRP characterized by decreased loading in inferior frontal cortex, striatum and cerebellum, and increased loading in sensorimotor, parietal and occipital cortices. MSAPRP scores discriminated between normal, MSA, PSP and PD subjects and correlated with standardized ratings of clinical stages and motor symptoms in MSA. High similarities in MSAPRPs, network scores and corresponding maps of metabolic abnormality were observed between two different cohorts. Conclusion: We have demonstrated reproducible metabolic topographies associated with MSA at both network and regional levels in two independent patient cohorts. Moreover, MSAPRP scores are sensitive for evaluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols

Positron emission tomography (Pet) and neuroimaging in the personalized approach to neurodegenerative causes of dementia

Generally, dementia should be considered an acquired syndrome, with multiple possible causes, rather than a specific disease in itself. The leading causes of dementia are neurodegenerative and non-neurodegenerative alterations. Nevertheless, the neurodegenerative group of diseases that lead to cognitive impairment and dementia includes multiple possibilities or mixed pathologies with personalized treatment management for each cause, even if Alzheimer's disease is the most common pathology. Therefore, an accurate differential diagnosis is mandatory in order to select the most appropriate therapy approach. The role of personalized assessment in the treatment of dementia is rapidly growing. Neuroimaging is an essential tool for differential diagnosis of multiple causes of dementia and allows a personalized diagnostic and therapeutic protocol based on risk factors that may improve treatment management, especially in early diagnosis during the prodromal stage. The utility of structural and functional imaging could be increased by standardization of acquisition and analysis methods and by the development of algorithms for automated assessment. The aim of this review is to focus on the most commonly used tracers for differential diagnosis in the dementia field. Particularly, we aim to explore F-18 Fluorodeoxyglucose (FDG) and amyloid positron emission tomography (PET) imaging in Alzheimer's disease and in other neurodegenerative causes of dementia

Positron emission tomography neuroimaging in neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis

Neurodegenerative diseases are a growing problem of ageing societies. Their insidious onset, and the lack of reliable biomarkers, result in significant diagnosis delays. This article summarises the results of studies on the use of positron emission tomography (PET) in the diagnosis of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. It focuses on clinical-pathogenetic aspects of individual diseases, as well as disease-specific patterns relevant in differential diagnosis and in assessing the risk of disease development and prognosis

Cerebral Metabolic Patterns In Neurodegeneration

Neurodegenerative disorders comprise a group of conditions, including Parkinson’s and Alzheimer’s disease, in which neurons in specific brain regions deteriorate. Different neurodegenerative diseases exhibit distinct patterns of brain damage. Despite this, they often present with similar features in the beginning, and a ‘typical’ clinical picture can take years to develop. Establishing a diagnosis early in the disease course can be challenging, even for experts. Brain imaging with 18F-FDG PET may offer a solution, as 18F-FDG PET can be used to identify areas with disrupted glucose metabolism caused by the underlying disease process. In this thesis, several distinguishable disease-related patterns were identified in 18F-FDG PET brain scans using a mathematical model called spatial covariance analysis. This model determines metabolic brain patterns by identifying areas of relative metabolic differences between healthy controls and patients. These patterns can be used to quantify the degree of disease activity in the brain scans of new patients. We investigated whether this method would be useful at the early stages of neurodegenerative disease. We studied patients with rapid eye movement sleep behavior disorder (RBD), an early stage of Parkinson’s disease. The Parkinson’s disease-related brain pattern was already present in the scans of RBD patients, even though these patients did not yet manifest typical parkinsonian motor symptoms. We also found that mildly cognitively impaired subjects expressed the Alzheimer’s disease-related brain pattern years before developing full-blown dementia. 18F-FDG PET is a widely-available modality which is valuable for the study of neurodegenerative disorders, especially when combined with advanced analytical techniques