Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis

Verstraete, Esther; Foerster, Bradley R.

doi:10.1007/s13311-015-0347-9

Cited by 28 publications

(16 citation statements)

References 119 publications

(130 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in contrast to the classical tenet that ALS represents the outcome of extensive and progressive impairment of a fixed set of motor connections, recent neuroimaging findings suggest that the disease spreads along vast non-motor connections. Indeed, advanced neuroimaging techniques, which allow for the non-invasive investigation of structural and functional brain organization, have so far introduced new opportunities for the study of ALS and are currently supporting the multi-systemic pathophysiology of this disease23.…”

mentioning

confidence: 99%

EEG functional network topology is associated with disability in patients with amyotrophic lateral sclerosis

Fraschini

Demuru

Hillebrand

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Amyotrophic Lateral Sclerosis (ALS) is one of the most severe neurodegenerative diseases, which is known to affect upper and lower motor neurons. In contrast to the classical tenet that ALS represents the outcome of extensive and progressive impairment of a fixed set of motor connections, recent neuroimaging findings suggest that the disease spreads along vast non-motor connections. Here, we hypothesised that functional network topology is perturbed in ALS, and that this reorganization is associated with disability. We tested this hypothesis in 21 patients affected by ALS at several stages of impairment using resting-state electroencephalography (EEG) and compared the results to 16 age-matched healthy controls. We estimated functional connectivity using the Phase Lag Index (PLI), and characterized the network topology using the minimum spanning tree (MST). We found a significant difference between groups in terms of MST dissimilarity and MST leaf fraction in the beta band. Moreover, some MST parameters (leaf, hierarchy and kappa) significantly correlated with disability. These findings suggest that the topology of resting-state functional networks in ALS is affected by the disease in relation to disability. EEG network analysis may be of help in monitoring and evaluating the clinical status of ALS patients.

show abstract

mentioning

confidence: 99%

EEG functional network topology is associated with disability in patients with amyotrophic lateral sclerosis

Fraschini

Demuru

Hillebrand

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Menke et al 8 have recently reported imaging abnormalities even before clinical symptoms, offering the potential for neuroprotective intervention, particularly in familial cases. Current literature points to DTI technique as the most promising candidate for imaging biomarker in ALS, able to elucidate the brain phenotype of ALS and also detect white matter tract changes in extramotor regions 8,10 .The results of Chaves et al 11 using a 1.5 Tesla MR equipment reinforce the clinical use of fractional anisotropy (FA) to detect extra-motor brain abnormalities in ALS patients. Despite this further multicenter validation with larger cohorts of patients remains mandatory prior to the integration of this technique into the clinical routine as biomarker able to contribute in standard clinical decision-making algorithms.…”

mentioning

confidence: 96%

“…A plausible biomarker for upper motor neuron degeneration in ALS is becoming tangible after recent advances in high-throughput MRI techniques, through which one can believe that we are going to the forefront of a breakthrough able to translate research findings into reliable clinical tests that will support the practice of personalized medicine 8,9,10 .…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Revealing the microstructural brain damage in amyotrophic lateral sclerosis: the relentless pursuit to approach an imaging biomarker

Rocha

Chieia

2017

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

A myotrophic lateral sclerosis (ALS) is the commonest clinical form of the wider neurodegenerative syndrome encompassed by the term motor neuron disease (MND). ALS has a consistent incidence of 1-2/100,000/year, and a lifetime risk estimated at 1 in 400. The disease is characterized by the progressive death of upper motor neurons (UMNs) of the cerebral primary motor cortex and corticospinal tract, in combination with degeneration of lower motor neurons (LMNs) whose origins lie in the brainstem and spinal anterior horns. Loss of motor neurons in general results in weakness, but specifically loss of LMNs results in secondary wasting of the downstream musculature and spasticity arises from loss of UMNs 1 .About 10% of cases are considered as being familial ( fALS), whereas the remaining 90% seem to occur sporadically (sALS) with no family history of ALS. Since the first discovery of SOD1 mutations being causative for ALS in 1993 2 , researchers all over the world have made great effort to further delineate the genetic basis underlying ALS. Today, more than 30 confirmed major disease genes are listed by the Amyotrophic Lateral Sclerosis Online genetics Database (ALSoD), the most frequently affected being C9orf72 (40% fALS, 5-6% sALS; pathogenic repeat expansion in the non-coding region between exons 1a and 1b, detection by repeat analysis), SOD1 (20% fALS, 3% sALS), FUS (5% fALS, <1% sALS) and TARDBP (3% fALS,2% sALS) 3 .In addition to this clinically heterogeneous syndrome a pathologically overlapping with frontotemporal dementia motor signs have been detected by neuropsychological tests in about 50% of sALS patients. Furthermore typical frontotemporal dementia (FTD) occurs in approximately 10% of the patients 4 , and the term frontotemporal dementia-motor neuron disease (FTD-MND) continuum was proposed to describe this association 4 , which occurs mostly in C9ORF72-linked fALS 5 .Despite all this clinical and etiopathogenic complexity, some faces of ALS, including FTD-MND continnum, have been elucidated by magnetic resonance imaging (MRI) techniques, which have proved to be useful to reveal microstructural brain abnormalities associated with different rates of symptom progression 6,7 . A plausible biomarker for upper motor neuron degeneration in ALS is becoming tangible after recent advances in high-throughput MRI techniques, through which one can believe that we are going to the forefront of a breakthrough able to translate research findings into reliable clinical tests that will support the practice of personalized medicine 8,9,10 .Advances in neuroimaging have enabled mapping of some endpoints in functional, structural, and molecular aspects of ALS pathology. Menke et al. 8 have recently reported imaging abnormalities even before clinical symptoms, offering the potential for neuroprotective intervention, particularly in familial cases. Current literature points to DTI technique as the most promising candidate for imaging biomarker in ALS, able to elucidate the brain phenotype of ALS and also detect white matter...

show abstract

“…Novel advances in neuroimaging are then reviewed by Drs. Esther Verstraete and Bradley Foerster [11], who present the clinical value of the various advanced neuroimaging modalities utilized to study ALS, discuss the potential of imaging to offer diagnostic and prognostic biomarkers, and introduce the remaining challenges underlying the translation and utility of neuroimaging in clinical applications and therapeutic trials. To end this section, Dr. Neta Zach et al [12] highlight the tremendous benefits of the Pooled Resource Open-access ALS Clinical Trials (PRO-ACT) database, a platform that currently contains data on the thousands of patients with ALS participating in 17 completed clinical trials, and incorporation of new patient and trial data is ongoing.…”

mentioning

confidence: 99%

The Spectrum of Motor Neuron Diseases: From Childhood Spinal Muscular Atrophy to Adult Amyotrophic Lateral Sclerosis

Sakowski

Feldman

2015

Neurotherapeutics

View full text Add to dashboard Cite

Since the topic of motor neuron diseases was last covered in Neurotherapeutics in 2008, increasing insight into genetic causes and underlying disease mechanisms has fueled several advances that have paved the way for new therapeutic strategies that are currently in development or being tested in clinical trials. In this special issue, we present reviews by leading investigators in the field that detail these advances for spinal muscular atrophy (SMA), an inherited neuromuscular disease associated with motor neuron degeneration and muscle atrophy that presents early in life, and amyotrophic lateral sclerosis (ALS), a fatal adult-onset neuromuscular disease also characterized by loss of motor neurons. The papers are divided into 4 main sections that cover 1) SMA advances, 2) ALS challenges and recent biological advances, 3) ALS clinical trial design considerations and outcome measures, and 4) emerging ALS treatments. Together, these articles offer a timely and comprehensive look into the recent research advances, current clinical considerations, and therapeutic prospects currently in development or being tested for motor neuron diseases.The issue begins with 2 papers focused on SMA. In the first article, Drs. Michelle Farrar and Matthew Kiernan [1] provide a detailed overview of the genetic basis of SMA forms and variants and present common pathophysiological mechanisms, including discussion of the function of the survival motor neuron protein. They then discuss considerations for therapeutic development and testing before reviewing potential molecular biomarkers for outcome assessments and trial design. Next, Drs. Constantin d'Ydewalle and Charlotte Sumner [2] present an eloquent synopsis of promising SMA treatments currently in advanced stages of development, a discussion that is prefaced by an overview of the available in vivo mouse SMA models. The treatment strategies include some originally designed for applications in ALS, approaches to induce survival motor neuron, and new treatment paradigms harnessing epigenetic targets, antisense oligonucleotides, and gene therapy approaches. Notably, both articles also discuss important issues that remain to be addressed for current progress, such as how well preclinical models recapitulate the human phenotype, how to factor in disease heterogeneity and identify and define potential therapeutic windows, and how to best analyze effects on disease progression. We believe the recent novel insights and current advances bode well for continued progress and the identification of much needed treatment options in SMA.The second section of the issue begins with a review by Drs. Jeffrey Rosenfeld and Michael Strong [3], which specifies the current challenges underlying therapeutic development that accompany the recent expansions in our understanding of the complex, multifaceted nature of ALS. Briefly, establishing firm diagnostic and prognostic criteria, determining what role frontotemporal dysfunction plays in the classification of ALS, identifying an accepted biomarker, determi...

show abstract

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis

Cited by 28 publications

References 119 publications

EEG functional network topology is associated with disability in patients with amyotrophic lateral sclerosis

EEG functional network topology is associated with disability in patients with amyotrophic lateral sclerosis

Revealing the microstructural brain damage in amyotrophic lateral sclerosis: the relentless pursuit to approach an imaging biomarker

The Spectrum of Motor Neuron Diseases: From Childhood Spinal Muscular Atrophy to Adult Amyotrophic Lateral Sclerosis

Contact Info

Product

Resources

About