Dataset Information

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of upper and lower motor neurons, with variable involvement of extramotor brain regions. Currently, there are no established objective markers of upper motor neuron and extramotor involvement in ALS. Here, we review the potential diagnostic value of advanced neuroimaging techniques that are increasingly being used to study the brain in ALS. First, we discuss the role of different imaging modalities in our increasing understanding of ALS pathogenesis, and their potential to contribute to objective upper motor neuron biomarkers for the disease. Second, we discuss the challenges to be overcome and the required phases of diagnostic test development to translate imaging technology to clinical care. We also present examples of multidimensional imaging approaches to achieve high levels of diagnostic accuracy. Last, we address the role of neuroimaging in clinical therapeutic trials. Advanced neuroimaging techniques will continue to develop and offer significant opportunities to facilitate the development of new effective treatments for ALS.

SUBMITTER: Verstraete E

PROVIDER: S-EPMC4404464 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis.

Verstraete Esther E Foerster Bradley R BR

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20150401 2

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of upper and lower motor neurons, with variable involvement of extramotor brain regions. Currently, there are no established objective markers of upper motor neuron and extramotor involvement in ALS. Here, we review the potential diagnostic value of advanced neuroimaging techniques that are increasingly being used to study the brain in ALS. First, we discuss the role of different imaging modalities in our increasing ...[more]

PMID: 25791072

Similar Datasets

Project description:Amyotrophic lateral sclerosis, when viewed as a biological entity rather than a clinical syndrome, probably evolves along a continuum, with the initial clinically silent phase eventually evolving into clinically manifest amyotrophic lateral sclerosis. Since motor neuron degeneration is incremental and cumulative over time, it stands to reason that the clinical syndrome of amyotrophic lateral sclerosis is probably preceded by a prodromal state characterized by minor motor abnormalities that are initially insufficient to permit a diagnosis of amyotrophic lateral sclerosis. This prodromal period, however, is usually missed, given the invariably long delays between symptom onset and diagnostic evaluation. The Pre-Symptomatic Familial ALS Study, a cohort study of pre-symptomatic gene mutation carriers, offers a unique opportunity to observe what is typically unseen. Here we describe the clinical characterization of 20 pre-symptomatic mutation carriers (in SOD1, FUS and C9orf72) whose phenoconversion to clinically manifest disease has been prospectively studied. In so doing, we observed a prodromal phase of mild motor impairment in 11 of 20 phenoconverters. Among the n = 12 SOD1 A4V mutation carriers, phenoconversion was characterized by abrupt onset of weakness, with a short (1-3.5 months) prodromal period observable in a small minority (n = 3); the observable prodrome invariably involved the lower motor neuron axis. By contrast, in all n = 3 SOD1 I113T mutation carriers, diffuse lower motor neuron and upper motor neuron signs evolved insidiously during a prodromal period that extended over a period of many years; prodromal manifestations eventually coalesced into a clinical syndrome that is recognizable as amyotrophic lateral sclerosis. Similarly, in all n = 3 C9orf72 hexanucleotide repeat expansion mutation carriers, focal or multifocal manifestations of disease evolved gradually over a prodromal period of 1-2 years. Clinically manifest ALS also emerged following a prodromal period of mild motor impairment, lasting >4 years and ∼9 months, respectively, in n = 2 with other gene mutations (SOD1 L106V and FUS c.521del6). On the basis of this empirical evidence, we conclude that mild motor impairment is an observable state that precedes clinically manifest disease in three of the most common genetic forms of amyotrophic lateral sclerosis (SOD1, FUS, C9orf72), and perhaps in all genetic amyotrophic lateral sclerosis; we also propose that this might be true of non-genetic amyotrophic lateral sclerosis. As a diagnostic label, mild motor impairment provides the language to describe the indeterminate (and sometimes intermediate) transition between the unaffected state and clinically manifest amyotrophic lateral sclerosis. Recognizing mild motor impairment as a distinct clinical entity should generate fresh urgency for developing biomarkers reflecting the earliest events in the degenerative cascade, with potential to reduce the diagnostic delay and to permit earlier therapeutic intervention.

Dataset Information

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis.

Publications

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets