Abstract
BackgroundThe spectrum of motor neuron disease (MND) includes numerous phenotypes with various life expectancies. The degree of upper and lower motor neuron involvement can impact prognosis. Phase sensitive inversion recovery (PSIR) imaging has been shown to detect in vivo gray matter (GM) and white matter (WM) atrophy in the spinal cord of other patient populations but has not been explored in MND.MethodsIn this study, total cord, WM and GM areas of ten patients with a diagnosis within the MND spectrum were compared to those of ten healthy controls (HC). Patients’ diagnosis included amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, primary muscular atrophy, facial onset sensory and motor neuronopathy and ALS-Frontotemporal dementia. Axial 2D PSIR images were acquired at four cervical disc levels (C2-C3, C3-C4, C5-C6 and C7-T1) with a short acquisition time (2 minutes) protocol. Total cross-sectional areas (TCA), GM and WM areas were measured using a combination of highly reliable manual and semi-automated methods. Cord areas in MND patients were compared with HC using linear regression analyses adjusted for age and sex. Correlation of WM and GM areas in MND patients was explored to gain insights into underlying atrophy patterns.ResultsMND patients as a group had significantly smaller cervical cord GM area compared to HC at all four levels (C2-C3: p = .009; C3-C4: p = .001; C5-C6: p = .006; C7-T1: p = .002). WM area at C5-C6 level was significantly smaller (p = .001). TCA was significantly smaller at C3-C4 (p = .018) and C5-C6 (p = .002). No significant GM and WM atrophy was detected in the two patients with predominantly bulbar phenotype. Concomitant GM and WM atrophy was detected in solely upper or lower motor neuron level phenotypes. There was a significant correlation between GM and WM areas at all four levels in this diverse population of MND.ConclusionSpinal cord GM and WM atrophy can be detected in vivo in patients within the MND spectrum using a short acquisition time 2D PSIR imaging protocol. PSIR imaging shows promise as a method for quantifying spinal cord involvement and thus may be useful for diagnosis, prognosis and for monitoring disease progression.
Highlights
The distinct spinal cord pathology of amyotrophic lateral sclerosis (ALS) was first described by Charcot over 100 years ago [1, 2]
Phase sensitive inversion recovery (PSIR) images acquired on 10 healthy controls (HC) to measure white matter (WM) and gray matter (GM) areas of the whole spinal cord and related data described in previous studies (S1 Table) were used for comparison with findings in the motor neuron disease (MND) group [28, 31]
Our findings suggest that the detection of GM and WM atrophy patterns could aid in a better classification of distinct MND phenotypes, that might arise from different underlying pathophysiological mechanisms
Summary
The distinct spinal cord pathology of amyotrophic lateral sclerosis (ALS) was first described by Charcot over 100 years ago [1, 2]. ALS is considered part of a larger heterogeneous spectrum of motor neuron diseases (MND) [3], that includes (but is not limited to): ALS, primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), ALS and frontotemporal dementia (ALS-FTD), and facial-onset sensory and motor neuronopathy (FOSMN) [3,4,5]. These four MND phenotypes have recently been associated with TDP-43 (transactive response DNAbinding protein 43) neuropathology found on autopsy, and it has been posited that they are linked as TDP-43 proteinopathies [2, 5]. Phase sensitive inversion recovery (PSIR) imaging has been shown to detect in vivo gray matter (GM) and white matter (WM) atrophy in the spinal cord of other patient populations but has not been explored in MND
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