Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease usually assumed to target motor neurons (MNs). However, evidence of involvement of other cells types, also outside the central nervous system, has challenged this neurocentric view of ALS, which may thus be defined a multi-systemic disease. Although muscle abnormalities in ALS are habitually considered secondary to MN damage, muscle, too, can be a primary target, with dying back degeneration of MNs occurring subsequently. In recent years, efforts to clarify the pathogenesis of ALS have focused on muscle tissue. Muscle magnetic resonance imaging (MRI), shown to be useful to define prognostic biomarkers of ALS in the G93A-SOD1 mouse model, is an established diagnostic tool in inherited and acquired neuromuscular disorders. Literature data on the role of muscle MRI in ALS are scarce and heterogeneous. To study the role of muscle MRI in the diagnosis and prognosis of ALS, we proposed two cross-sectional and one longitudinal studies. In the first study we compared qualitative T1-w images of hand, paraspinal and lower limb muscles in newly diagnosed ALS patients and in age-matched healthy controls (HCs) to look for evidence of muscular atrophy and remodelling (i.e. fatty substitution) and to relate the radiological findings to clinical and electromyographic (EMG) data. We concluded that muscle T1-w MRI can distinguish ALS patients from HCs for specific regions (i.e. legs). MRI abnormalities could be found in pauci-symptomatic spinal muscles in bulbar-onset patients (i.e. iliopsoas). Paraspinal and leg muscles MRI may be a useful diagnostic tool in early ALS. Form these preliminary results, we planned to conduct a longitudinal study in order to investigate more in deep the role of muscle through MRI measurements as a prognostic or predictive biomarker in ALS patients. In the second part we decided to focus the study on the role of paraspinal MRI in the diagnosis of ALS, and we qualitatively compared T1-w images in newly diagnosed ALS patients, age-matched healthy controls, patients affected by inflammatory myopathy and lumbar radiculopathy. We found that paraspinal T1-w MRI could help to distinguish spinal ALS patients from healthy and pathological controls. In particular, study of longissimus dorsi can play the role of diagnostic ALS biomarker. In the third study we compared quantitative images (6-point Dixon GRE and multi-echo TSE T2-w obtaining Water T2 and Fat Fraction values) of lower limb muscles in ALS patients at different timepoints to look for evidence of disease progression and to relate the radiological findings to clinical data. We found that ALS patients showed acute alterations in muscles more than controls at baseline but not at following timepoints. Moreover, ALS patients and controls had no difference in fat fraction at baseline, but the difference is significant during the follow up. In conclusion, MRI pattern traces the pathological process of ALS and muscle MRI can be useful as prognostic biomarker.

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Identification of muscular MRI biomarkers in Amyotrophic Lateral Sclerosis (ALS)

DIAMANTI, LUCA
2019

Abstract

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Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease usually assumed to target motor neurons (MNs). However, evidence of involvement of other cells types, also outside the central nervous system, has challenged this neurocentric view of ALS, which may thus be defined a multi-systemic disease. Although muscle abnormalities in ALS are habitually considered secondary to MN damage, muscle, too, can be a primary target, with dying back degeneration of MNs occurring subsequently. In recent years, efforts to clarify the pathogenesis of ALS have focused on muscle tissue. Muscle magnetic resonance imaging (MRI), shown to be useful to define prognostic biomarkers of ALS in the G93A-SOD1 mouse model, is an established diagnostic tool in inherited and acquired neuromuscular disorders. Literature data on the role of muscle MRI in ALS are scarce and heterogeneous. To study the role of muscle MRI in the diagnosis and prognosis of ALS, we proposed two cross-sectional and one longitudinal studies. In the first study we compared qualitative T1-w images of hand, paraspinal and lower limb muscles in newly diagnosed ALS patients and in age-matched healthy controls (HCs) to look for evidence of muscular atrophy and remodelling (i.e. fatty substitution) and to relate the radiological findings to clinical and electromyographic (EMG) data. We concluded that muscle T1-w MRI can distinguish ALS patients from HCs for specific regions (i.e. legs). MRI abnormalities could be found in pauci-symptomatic spinal muscles in bulbar-onset patients (i.e. iliopsoas). Paraspinal and leg muscles MRI may be a useful diagnostic tool in early ALS. Form these preliminary results, we planned to conduct a longitudinal study in order to investigate more in deep the role of muscle through MRI measurements as a prognostic or predictive biomarker in ALS patients. In the second part we decided to focus the study on the role of paraspinal MRI in the diagnosis of ALS, and we qualitatively compared T1-w images in newly diagnosed ALS patients, age-matched healthy controls, patients affected by inflammatory myopathy and lumbar radiculopathy. We found that paraspinal T1-w MRI could help to distinguish spinal ALS patients from healthy and pathological controls. In particular, study of longissimus dorsi can play the role of diagnostic ALS biomarker. In the third study we compared quantitative images (6-point Dixon GRE and multi-echo TSE T2-w obtaining Water T2 and Fat Fraction values) of lower limb muscles in ALS patients at different timepoints to look for evidence of disease progression and to relate the radiological findings to clinical data. We found that ALS patients showed acute alterations in muscles more than controls at baseline but not at following timepoints. Moreover, ALS patients and controls had no difference in fat fraction at baseline, but the difference is significant during the follow up. In conclusion, MRI pattern traces the pathological process of ALS and muscle MRI can be useful as prognostic biomarker.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1301269
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