Neurodegenerative Disease Amyotrophic Lateral Sclerosis Neuroimaging Advances in Amyotrophic Lateral Sclerosis Dorothée Lulé Senior Research Scientist, Section of Neurophysiology, Department of Neurology, University of Ulm

Abstract

The development of non-invasive functional imaging techniques has allowed neuroscientists to investigate the physiological parameters of the clinical features of amyotrophic lateral sclerosis (ALS), a severe neurological disease. Modern neuroimaging techniques enable anatomy and function to be connected in vivo with an acceptable balance between low patient load and high information capacity, making them ideal for clinical research in patients with physical restrictions, such as those with ALS. Structural imaging techniques in ALS include T1/T2-weighted structural magnetic resonance imaging, diffusion tensor imaging and voxel-based morphometry. Functional neuroimaging enables the acquisition of dynamic cortical function either in a passive (or resting) state or via active paradigms. The main technique used is functional magnetic resonance imaging. Structural and functional neuroimaging has provided evidence of alterations in motor and non-motor cortical pathways in ALS. In the future, neuroimaging may provide early diagnostic criteria to support the clinical diagnosis of ALS, help us to understand the aetiological background of the disease and pave the way for a new viewpoint on the functional capacities of these patients, which may have a major impact on our way of thinking about end-of-life decisions.

Keywords Functional magnetic resonance imaging, amyotrophic lateral sclerosis (ALS), neuroimaging

Disclosure: The author has no conflicts of interest to declare. Received: 27 September 2010 Accepted: 15 November 2010 Citation: European Neurological Review, 2010;5(2):54–8 Correspondence: Dorothée Lulé, Section of Neurophysiology, Department of Neurology, University of Ulm, Albert-Einstein-Allee 47, 89081 Ulm, Germany. E: dorothee.lule@uni-ulm.de

Neuroimaging opens the possibility of non-invasive investigation of structural and dynamic processes in the human brain in vivo. It is a helpful tool to explore the impact of structural and functional changes at the cortical and subcortical level in different neurological and psychiatric pathologies. Magnetic resonance imaging (MRI) with its various applications is one of the leading technologies in this field. MR neuroimaging may be used on the one hand for diagnostic procedures and on the other hand for analysis of structural and functional cortical networks. Conventional cortical (and cervical) MRI techniques are complemented by volumetric and morphometric analysis of 3D MRI data (e.g. voxel-based morphometry [VBM]), proton MR spectroscopy (MRS), diffusion tensor imaging (DTI) and functional imaging methods such as functional MRI (fMRI).

There have been extensive advances in computer-based and conventional neuroimaging in motor neuron diseases (MNDs) such as ALS; however, standard protocols for clinical diagnosis and biomarkers are still lacking and work is still in progress. Neuroimaging can make a substantial contribution to clinical evaluation and diagnostic findings. Structural and functional neuroimaging may provide an objective marker for monitoring disease progression and the modifying effect of potential treatments.

For the last decade, advanced acquisition and post-processing techniques have led to a considerable increase in the number of structural and functional studies in severely restricted patients such

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as those with ALS. This article will evaluate the use of neuroimaging in the clinical setting for ALS/MND.

Amyotrophic Lateral Sclerosis

ALS is the most common adult-onset MND. It is characterised by a relentless progressive waste of motor neuron function leading to loss of mobility and verbal communication. The disease terminates in a so-called ‘locked-in’ state where cognitive functions are mostly preserved but afferent and efferent information flow is reduced to a minimum. Autonomous and sensory nervous system function is usually only mildly affected, and sphincter and ocular function is preserved for the the longest. Upper and lower motor neurons are affected in the course of the disease; however, onset of symptoms is usually restricted to either upper or lower motor neurons, i.e. the disease starts either with weakness of the arms or legs (‘spinal’ onset, mostly lateralised to one side) or with speaking and swallowing difficulties (‘bulbar’ onset). Patients die within three to five years, usually from breathing difficulties, unless appropriate measures such as mechanical ventilation and parenteral nutrition are taken.

About 10% of patients present a genetic background, and 10–20% of these genetically determined cases present a mutation in the SOD-1 enzyme. Over the last few years, evidence has emerged supporting the involvement of other genes that seem to be causally linked to ALS, such as dynactin, senataxin, TDP-43 and FUS. In most patients, the aetiology of the disease is unknown.

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