Dissociation of structural and functional integrities of the motor system in amyotrophic lateral sclerosis and behavioral-variant frontotemporal dementia

Background and Purpose: This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). Methods: Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. Results: The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. Conclusions: Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders

Neural indicators of fatigue in chronic diseases : A systematic review of MRI studies

The authors would like to thank the Sir Jules Thorn Charitable Trust for their financial support.Peer reviewedPublisher PD

Occasional essay: upper motor neuron syndrome in amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) requires recognition of both lower (LMN) and upper motor neuron (UMN) dysfunction.1 However, classical UMN signs are frequently difficult to identify in ALS.2 LMN involvement is sensitively detected by electromyography (EMG)3 but, as yet, there are no generally accepted markers for monitoring UMN abnormalities,4 the neurobiology of ALS itself, and disease spread through the brain and spinal cord,.5 Full clinical assessment is therefore necessary to exclude other diagnoses and to monitor disease progression. In part, this difficulty regarding detection of UMN involvement in ALS derives from the definition of ‘the UMN syndrome’. Abnormalities of motor control in ALS require reformulation within an expanded concept of the UMN, together with the neuropathological, neuro-imaging and neurophysiological abnormalities in ALS. We review these issues here

Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis

Objective Reliable biomarkers for amyotrophic lateral sclerosis ( ALS ) are needed, given the clinical heterogeneity of the disease. Here, we provide proof‐of‐concept for using multimodal magnetic resonance imaging ( MRI ) as a diagnostic biomarker for ALS . Specifically, we evaluated the added diagnostic utility of proton magnetic resonance spectroscopy ( MRS ) to diffusion tensor imaging ( DTI ). Methods Twenty‐nine patients with ALS and 30 age‐ and gender‐matched healthy controls underwent brain MRI which used proton MRS including spectral editing techniques to measure γ‐aminobutyric acid ( GABA ) and DTI to measure fractional anisotropy of the corticospinal tract. Data were analyzed using logistic regression, t ‐tests, and generalized linear models with leave‐one‐out analysis to generate and compare the resulting receiver operating characteristic ( ROC ) curves. Results The diagnostic accuracy is significantly improved when the MRS data were combined with the DTI data as compared to the DTI data only (area under the ROC curves ( AUC ) = 0.93 vs. AUC  = 0.81; P  = 0.05). The combined MRS and DTI data resulted in sensitivity of 0.93, specificity of 0.85, positive likelihood ratio of 6.20, and negative likelihood ratio of 0.08 whereas the DTI data only resulted in sensitivity of 0.86, specificity of 0.70, positive likelihood ratio of 2.87, and negative likelihood ratio of 0.20. Interpretation Combining multiple advanced neuroimaging modalities significantly improves disease discrimination between ALS patients and healthy controls. These results provide an important step toward advancing a multimodal MRI approach along the diagnostic test development pathway for ALS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106065/1/acn330.pd

Structural magnetic resonance imaging findings and histopathological correlations in motor neuron diseases—A systematic review and meta-analysis

OBJECTIVES The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation. METHODS In a comprehensive literature search, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. 21 records were included in a random effect model meta-analysis. RESULTS Our meta-analysis shows that both T2-hyperintensities along the corticospinal tracts (CST) and motor cortex T2$^{*}$-hypointensitites, also called "motor band sign", are more prevalent in ALS patients compared to controls [OR 2.21 (95%-CI: 1.40-3.49) and 10.85 (95%-CI: 3.74-31.44), respectively]. These two imaging findings correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology, respectively. Additionally, certain clinical MND phenotypes such as amyotrophic lateral sclerosis (ALS) seem to present with distinct CNS atrophy patterns. CONCLUSIONS Although CST T2-hyperintensities and the "motor band sign" are non-specific imaging features, they can be leveraged for diagnostic workup of suspected MND cases, together with certain brain atrophy patterns. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182682

Imaging techniques in ALS.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of both upper and lower motor neuron located in the spinal cord and brainstem. Diagnosis of ALS is predominantly clinical, nevertheless, electromyography and Magnetic Resonance Imaging (MRI) may provide support. Several advanced MRI techniques have been proven useful for ALS diagnosis and, indeed, the combination of different MRI techniques demonstrated an improvement in sensitivity and specificity as far as 90%. This review focus on the imaging techniques currently used in the diagnosis and management of ALS with brief considerations on future applications

Emerging magnetic resonance imaging techniques and analysis methods in amyotrophic lateral sclerosis

Objective markers of disease sensitive to the clinical activity, symptomatic progression, and underlying substrates of neurodegeneration are highly coveted in amyotrophic lateral sclerosis in order to more eloquently stratify the highly heterogeneous phenotype and facilitate the discovery of effective disease modifying treatments for patients. Magnetic resonance imaging (MRI) is a promising, non-invasive biomarker candidate whose acquisition techniques and analysis methods are undergoing constant evolution in the pursuit of parameters which more closely represent biologically-applicable tissue changes. Neurite Orientation Dispersion and Density Imaging (NODDI; a form of diffusion imaging), and quantitative Magnetization Transfer Imaging (qMTi) are two such emerging modalities which have each broadened the understanding of other neurological disorders and have the potential to provide new insights into structural alterations initiated by the disease process in ALS. Furthermore, novel neuroimaging data analysis approaches such as Event-Based Modeling (EBM) may be able to circumvent the requirement for longitudinal scanning as a means to comprehend the dynamic stages of neurodegeneration . Combining these and other innovative imaging protocols with more sophisticated techniques to analyse ever-increasing datasets holds the exciting prospect of transforming understanding of the biological processes and temporal evolution of the ALS syndrome, and can only benefit from multicentre collaboration across the entire ALS research community

Neuroimaging biomarkers of neurodegenerative diseases and dementia

Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer's disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson's disease with and without dementia, dementia with Lewy bodies, Huntington's disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders