Spinal Cord Imaging in Amyotrophic Lateral Sclerosis: Historical Concepts—Novel Techniques

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neuron disease with no effective disease modifying therapies at present. Spinal cord degeneration is a hallmark feature of ALS, highlighted in the earliest descriptions of the disease by Lockhart Clarke and Jean-Martin Charcot. The anterior horns and corticospinal tracts are invariably affected in ALS, but up to recently it has been notoriously challenging to detect and characterize spinal pathology in vivo . With recent technological advances, spinal imaging now offers unique opportunities to appraise lower motor neuron degeneration, sensory involvement, metabolic alterations, and interneuron pathology in ALS. Quantitative spinal imaging in ALS has now been used in cross-sectional and longitudinal study designs, applied to presymptomatic mutation carriers, and utilized in machine learning applications. Despite its enormous clinical and academic potential, a number of physiological, technological, and methodological challenges limit the routine use of computational spinal imaging in ALS. In this review, we provide a comprehensive overview of emerging spinal cord imaging methods and discuss their advantages, drawbacks, and biomarker potential in clinical applications, clinical trial settings, monitoring, and prognostic roles.

Post-polio Syndrome: More Than Just a Lower Motor Neuron Disease

“…There have also been rare reports of polio patients developing ALS with characteristic histopathological findings (54, 55). Compared to other motor neuron diseases (56), there is a striking paucity of brain (57) and spinal cord imaging studies in PPS (58). Magnetic resonance imaging (MRI) has been used to evaluate volumetric changes (59) and to correlate anatomical changes to post mortem findings (48).…”

“…CSF sampling and muscle biopsy also allows the exclusion of other neuromuscular mimics. People with PPS typically undergo detailed spinal imaging to rule out alternative structural, neoplastic, compressive, or inflammatory spinal etiologies which could manifest in lower motor neuron dysfunction (58, 68–70). Electromyography (EMG) is an invaluable tool to assess suspected post-polio cases, as it allows the confirmation of a prior history of poliomyelitis while excluding differential diagnoses (71).…”

Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients

“…Progressive death of motor neurons in ALS leads to observable changes in the brain and spinal cord as highlighted by El Mendili et al 2019 [40]. Longitudinal studies have established a connection between cervical spinal cord atrophy and functional decline in ALS patients [41][42][43].…”

Brainstem pathology in amyotrophic lateral sclerosis and primary lateral sclerosis: A longitudinal neuroimaging study

“…Some of the barriers to the development of effective pharmacological interventions include the considerable clinical heterogeneity of the condition, lack of validated biomarkers and late recruitment into pharmacological trials (Mitsumoto et al., 2014; Schuster et al., 2015; Hardiman et al., 2016). The majority of imaging studies in MND focus on cortical grey matter atrophy (Omer et al., 2017; Bede et al., 2013a), corticospinal tract degeneration (Schuster et al., 2016a), corpus callosum pathology (Filippini et al., 2010; Bede et al., 2015) and spinal cord degeneration (Bede et al., 2012; El Mendili et al., 2019; Lebouteux et al., 2014). With the recognition of extra-motor deficits in MND (Burke, 2017; Elamin et al., 2017; Burke et al., 2016; Christidi et al., 2018; Finegan et al., 2019a) the frontotemporal (Nasseroleslami et al., 2019; Iyer, 2017), basal ganglia (Feron et al., 2018; Christidi et al., 2019) and cerebellar (Abidi et al., 2019) profiles of MNDs have also been gradually characterised (Bede et al., 2018a), but there remains a striking lack of dedicated brainstem studies.…”