Myelin imaging in amyotrophic and primary lateral sclerosis

Abstract

Primary lateral sclerosis (PLS) has been regarded as a rare, extreme form of amyotrophic lateral sclerosis (ALS). Like ALS, it is a clinical diagnosis without established biomarkers. We sought to explore loss of cerebral myelin in relation to clinical features, including cognitive impairment, in cases of both ALS and PLS.A novel MRI sequence (mcDESPOT) sensitive to water pools within myelin and intra- and extra-cellular spaces was applied to 23 ALS patients, seven PLS patients and 12 healthy controls, with interval follow-up in 15 ALS and four PLS patients.Results demonstrated that PLS patients were distinguished by widespread cerebral myelin water fraction reductions, independent of disease duration and clinical upper motor neuron burden. ALS patients showed a significant increase in intra- and extra-cellular water, indirectly linked to neuroinflammatory activity. Limited measures of cognitive impairment in the ALS group were associated with myelin changes within the anterior corpus callosum and frontal lobe projections. Longitudinal changes were only significant in the PLS group. In conclusion, in this exploratory study, myelin imaging has potential to distinguish PLS from ALS, and may have value as a marker of extramotor involvement. PLS may be a more active cerebral pathological process than its rate of clinical deterioration suggests.

Histological–MRI correlation in the primary motor cortex of patients with amyotrophic lateral sclerosis

“…Astrocyte proliferation and reactive state are increased in the ALS tissue, also in agreement with previous research (20)(21)(22)(23)(24). Myelin examination reveals changes in structure which are supported by transgenic rat and ALS imaging studies (25,26). These three factors, cellular architecture, astrogliosis, and myelination, all synergistically contribute to alterations in T 1 relaxation and T 1 -weighted contrast through a relaxation component model into which water may be distributed (extracellular, cytoplasmic, and vesicular) and the state (free, structured, and bound) in which the water is bound to the surrounding tissue.…”

Histological–MRI correlation in the primary motor cortex of patients with amyotrophic lateral sclerosis

“…Astrocyte proliferation and reactive state are increased in the ALS tissue, also in agreement with previous research (20)(21)(22)(23)(24). Myelin examination reveals changes in structure which are supported by transgenic rat and ALS imaging studies (25,26). These three factors, cellular architecture, astrogliosis, and myelination, all synergistically contribute to alterations in T 1 relaxation and T 1 -weighted contrast through a relaxation component model into which water may be distributed (extracellular, cytoplasmic, and vesicular) and the state (free, structured, and bound) in which the water is bound to the surrounding tissue.…”

Quantitative FLAIR MRI in Amyotrophic Lateral Sclerosis

“…We have previously found the posterior limb of the internal capsule to have value in stratifying ALS patients using DTI (36) , whereas the body of the CC and the corona radiata showed the greatest progressive changes in FLAIR intensity, with the cerebral peduncles providing diagnostic discrimination. The finding of highest FLAIR intensities in PLS patients, particularly in the CC, is of note building on other neuroimaging research findings in this subgroup 32 , 37 , 38 , 39 , 40 , 41 . There is a need for earlier diagnosis in PLS patients to improve the feasibility of earlier therapeutic intervention as well as care planning.…”

Hereditary primary lateral sclerosis and progressive nonfluent aphasia

“…MRI demonstrated dilation of central sulci in this series [as reported in PLS], enlarged frontoparietal sulci and lateral ventricles, bilateral white matter abnormalities in the corona radiata and atrophy of the corpus callosum; the last two have been associated with PLS and PPA [2,35,56,63]. In addition, impairment in memory, executive and language test scores in PLS, has been found to correlate with white matter tract damage on diffusion-tensor MRI [7,45].…”

Histological–MRI correlation in the primary motor cortex of patients with amyotrophic lateral sclerosis

“…Astrocyte proliferation and reactive state are increased in the ALS tissue, also in agreement with previous research (20)(21)(22)(23)(24). Myelin examination reveals changes in structure which are supported by transgenic rat and ALS imaging studies (25,26). These three factors, cellular architecture, astrogliosis, and myelination, all synergistically contribute to alterations in T 1 relaxation and T 1 -weighted contrast through a relaxation component model into which water may be distributed (extracellular, cytoplasmic, and vesicular) and the state (free, structured, and bound) in which the water is bound to the surrounding tissue.…”

Quantitative FLAIR MRI in Amyotrophic Lateral Sclerosis

“…We have previously found the posterior limb of the internal capsule to have value in stratifying ALS patients using DTI (36) , whereas the body of the CC and the corona radiata showed the greatest progressive changes in FLAIR intensity, with the cerebral peduncles providing diagnostic discrimination. The finding of highest FLAIR intensities in PLS patients, particularly in the CC, is of note building on other neuroimaging research findings in this subgroup 32 , 37 , 38 , 39 , 40 , 41 . There is a need for earlier diagnosis in PLS patients to improve the feasibility of earlier therapeutic intervention as well as care planning.…”

Hereditary primary lateral sclerosis and progressive nonfluent aphasia

“…MRI demonstrated dilation of central sulci in this series [as reported in PLS], enlarged frontoparietal sulci and lateral ventricles, bilateral white matter abnormalities in the corona radiata and atrophy of the corpus callosum; the last two have been associated with PLS and PPA [2,35,56,63]. In addition, impairment in memory, executive and language test scores in PLS, has been found to correlate with white matter tract damage on diffusion-tensor MRI [7,45].…”

Histological–MRI correlation in the primary motor cortex of patients with amyotrophic lateral sclerosis

“…Astrocyte proliferation and reactive state are increased in the ALS tissue, also in agreement with previous research (20)(21)(22)(23)(24). Myelin examination reveals changes in structure which are supported by transgenic rat and ALS imaging studies (25,26). These three factors, cellular architecture, astrogliosis, and myelination, all synergistically contribute to alterations in T 1 relaxation and T 1 -weighted contrast through a relaxation component model into which water may be distributed (extracellular, cytoplasmic, and vesicular) and the state (free, structured, and bound) in which the water is bound to the surrounding tissue.…”

Quantitative FLAIR MRI in Amyotrophic Lateral Sclerosis

“…We have previously found the posterior limb of the internal capsule to have value in stratifying ALS patients using DTI (36) , whereas the body of the CC and the corona radiata showed the greatest progressive changes in FLAIR intensity, with the cerebral peduncles providing diagnostic discrimination. The finding of highest FLAIR intensities in PLS patients, particularly in the CC, is of note building on other neuroimaging research findings in this subgroup 32 , 37 , 38 , 39 , 40 , 41 . There is a need for earlier diagnosis in PLS patients to improve the feasibility of earlier therapeutic intervention as well as care planning.…”

Hereditary primary lateral sclerosis and progressive nonfluent aphasia

“…MRI demonstrated dilation of central sulci in this series [as reported in PLS], enlarged frontoparietal sulci and lateral ventricles, bilateral white matter abnormalities in the corona radiata and atrophy of the corpus callosum; the last two have been associated with PLS and PPA [2,35,56,63]. In addition, impairment in memory, executive and language test scores in PLS, has been found to correlate with white matter tract damage on diffusion-tensor MRI [7,45].…”