Myelin imaging in amyotrophic and primary lateral sclerosis

Shannon Kolind,Rakesh Sharma,Steven Knight,Heidi Johansen-Berg,Kevin Talbot,Martin R Turner

doi:10.3109/21678421.2013.794843

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.

Highlights

IntroductionCharcot’s pivotal observation of the pallor of the corticospinal tracts (CSTs) forms the diagnostic cornerstone of amyotrophic lateral sclerosis (ALS) as a neurodegenerative syndrome characterized by progressive loss of both upper motor neurons (UMNs) of the corticospinal tract (CST), and lower motor neurons (LMNs) arising from the brainstem and spinal anterior horns
Results demonstrated that primary lateral sclerosis (PLS) patients were distinguished by widespread cerebral myelin water fraction reductions, independent of disease duration and clinical upper motor neuron burden
Limited measures of cognitive impairment in the amyotrophic lateral sclerosis (ALS) group were associated with myelin changes within the anterior corpus callosum and frontal lobe projections

Summary

Introduction

Charcot’s pivotal observation of the pallor of the corticospinal tracts (CSTs) forms the diagnostic cornerstone of amyotrophic lateral sclerosis (ALS) as a neurodegenerative syndrome characterized by progressive loss of both upper motor neurons (UMNs) of the corticospinal tract (CST), and lower motor neurons (LMNs) arising from the brainstem and spinal anterior horns. A small proportion who manifest solely UMN signs clinically, typically of lower limb-onset, are termed primary lateral sclerosis (PLS). This syndrome was first recognized by Erb [2] before clinicopathological papers defined the association with a consistently slower progression and survival typically. PLS is a clinical diagnosis, defined as UMN-only involvement for at least four years from symptom onset [5]. In its course PLS is difficult to distinguish from the ALS clinical sub-type of ‘UMN-predominant’ ALS, which has a consistently slower-than-average rate of progression [6]

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Conclusion