Kinnier Wilson’s puzzling features of amyotrophic lateral sclerosis

Turner, Martin R; Eisen, Andrew; Kiernan, Matthew C.; Ravits, John; Swash, Michael

doi:10.1136/jnnp-2017-317217

Cited by 4 publications

(2 citation statements)

References 103 publications

(73 reference statements)

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“…Another possible interpretation is that ALS begins within the muscle cells or at the neuromuscular junction. This hypothesis of “dying‐back” proposes that there is a spread of pathology from LMN to UMN, 29,30 which corroborates the idea of a less marked disease burden in LMNp patients.…”

Section: Discussionsupporting

confidence: 57%

Neural Correlates of Motor Imagery of Gait in Amyotrophic Lateral Sclerosis

Abidi

Marco

Grami

et al. 2020

Magnetic Resonance Imaging

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Background: Gait impairment is poorly characterized in amyotrophic lateral sclerosis (ALS), despite increasing evidence of extrapyramidal and cerebellar dysfunction. Gait impairment adds to the considerable motor disability of ALS patients and requires targeted multidisciplinary interventions. Purpose: To assess gait imagery-specific networks and functional adaptation in ALS. Study Type: Prospective. Population: Seventeen ALS patients with lower motor neuron predominant (LMNp) disability, 14 patients with upper motor neurons predominant (UMNp) disease, and 14 healthy controls were included. Field Strength/Sequences: 3T / gradient echo echo planar (GE-EPI). Assessment: Subjects performed a dual motor imagery task: normal and precision gait. The Movement Imagery Questionnaire-Revised Second Version (MIQ-rs) was used to appraise movement imagery in each participant. Study group-specific activation patterns were evaluated during motor imagery of gait. Additional generalized psychophysiological interaction analyses were carried out using the supplementary motor area, caudate, cerebellum, and superior parietal lobule as seed regions. Statistical Tests: Repeated-measures analysis of variance (ANOVA) was used to compare time imagery and MIQ-rs scores between groups. Size effects were also reported as partial eta squared (η2). One-way ANOVA was performed to explore differences in terms of connexions during motor imagery tasks. Results: A significant increase in imagery time in UMNp patients compared to controls (P < 0.05) and LMNp (P < 0.05) during imagined gait was demonstrated. UMNp patients exhibited altered supplementary motor area, precentral gyrus, superior parietal lobule, and dorsolateral prefrontal cortex activation and increased orbitofrontal (pFDR (False Discovery Rate) < 0.05), posterior parietal (pFDR < 0.05) caudate (pFDR < 0.05), and cerebellar (pFDR < 0.05) signal during imagined locomotion. Increased effective connectivity of the striato-cerebellar and parieto-cerebellar circuits was also demonstrated. Additional activation was detected in the insula and cingulate cortex. Data Conclusion: Enhanced striato-and parieto-cerebellar networks in UMNp ALS patients are likely to represent a compensatory response to impaired postural control. Level of Evidence: 2 Technical Efficacy Stage: 5

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Section: Discussionsupporting

confidence: 57%

Neural Correlates of Motor Imagery of Gait in Amyotrophic Lateral Sclerosis

Abidi

Marco

Grami

et al. 2020

Magnetic Resonance Imaging

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“…However, the question of where disease begins remains controversial because many researchers still favor the “dying-back” hypothesis, in which ALS begins within the muscle cells or at the NMJ. This hypothesis proposes that there is a spread of pathology from LMNs to UMNs (Chou and Norris, 1993; Fischer et al, 2004; Pun et al, 2006; Turner et al, 2018), or else, a simultaneous involvement of both UMNS and LMNs (Turner et al, 2018). Whilst most of the evidence for the dying-back mechanism comes from animal models, studies of muscle biopsies from early stage ALS patients and long-term survivors have demonstrated significant morphological abnormalities and major denervation/re-innervation at the NMJ, implying that this region is targeted early in disease (Millecamps et al, 2010; reviewed in Arbour et al, 2017).…”

Section: Network-driven Mn Vulnerabilitymentioning

confidence: 99%

Motor Neuron Susceptibility in ALS/FTD

et al. 2019

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of both upper and lower motor neurons (MNs) in the brain, brainstem and spinal cord. The neurodegenerative mechanisms leading to MN loss in ALS are not fully understood. Importantly, the reasons why MNs are specifically targeted in this disorder are unclear, when the proteins associated genetically or pathologically with ALS are expressed ubiquitously. Furthermore, MNs themselves are not affected equally; specific MNs subpopulations are more susceptible than others in both animal models and human patients. Corticospinal MNs and lower somatic MNs, which innervate voluntary muscles, degenerate more readily than specific subgroups of lower MNs, which remain resistant to degeneration, reflecting the clinical manifestations of ALS. In this review, we discuss the possible factors intrinsic to MNs that render them uniquely susceptible to neurodegeneration in ALS. We also speculate why some MN subpopulations are more vulnerable than others, focusing on both their molecular and physiological properties. Finally, we review the anatomical network and neuronal microenvironment as determinants of MN subtype vulnerability and hence the progression of ALS.

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Diagnostic criteria for amyotrophic lateral sclerosis

Timmins,

Thompson,

Kiernan

2024

Current Opinion in Neurology

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Purpose of review The present review will discuss the evolution of diagnostic criteria for amyotrophic lateral sclerosis (ALS) and biomarker considerations. Recent findings To address the limitations of existing ALS diagnostic criteria, a consortium of key stakeholders developed the Gold Coast consensus criteria (GCC). The GCC has similar or greater sensitivity compared with the revised El Escorial (rEEC) and Awaji criteria (AC), particularly for atypical phenotypes, maintained across disease duration, severity, and site of onset. In addition to improving diagnostic sensitivity, using the GCC in clinical trials may promote an increased enrolment of up to 50% of ALS patients who do not currently meet the full diagnostic eligibility requirements of the rEEC. Future inclusion of genetic biomarkers may mitigate some limitations of the GCC, to further improve diagnostic utility. In advance of such a process, validation of these biomarkers will be required before inclusion as additional criteria. Summary The GCC are simpler to use than previous consensus criteria, with demonstrated greater sensitivity and, enabling an earlier and more definitive ALS diagnosis, thereby facilitating wider enrolment into clinical trials. Broader implementation of the GCC in clinical trial settings is currently underway, globally.

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Kinnier Wilson’s puzzling features of amyotrophic lateral sclerosis

Cited by 4 publications

References 103 publications

Neural Correlates of Motor Imagery of Gait in Amyotrophic Lateral Sclerosis

Neural Correlates of Motor Imagery of Gait in Amyotrophic Lateral Sclerosis

Motor Neuron Susceptibility in ALS/FTD

Diagnostic criteria for amyotrophic lateral sclerosis

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