Objective A recent neuroanatomical staging scheme of amyotrophic lateral sclerosis (ALS) indicates that a cortical lesion may spread, as a network disorder, both at the cortical level and via corticofugal tracts, including corticospinal projections providing direct monosynaptic input to α-motoneurons. These projections are involved preferentially and early in ALS. If these findings are clinically relevant, the pattern of paresis in ALS should primarily involve those muscle groups that receive the strongest direct corticomotoneuronal (CM) innervation.
Methods In a large cohort (N=436), we analysed retrospectively the pattern of muscle paresis in patients with ALS using the UK Medical Research Council (MRC) scoring system; we subsequently carried out two independent prospective studies in two smaller groups (N=92 and N=54).
Results The results indicated that a characteristic pattern of paresis exists. When pairs of muscle groups were compared within patients, the group known to receive the more pronounced CM connections was significantly weaker. Within patients, there was greater relative weakness (lower MRC score) in thumb abductors versus elbow extensors, for hand extensors versus hand flexors and for elbow flexors versus elbow extensors. In the lower limb, knee flexors were relatively weaker than extensors, and plantar extensors were weaker than plantar flexors.
Conclusions These findings were mostly significant (p<0.01) for all six pairs of muscles tested and provide indirect support for the concept that ALS may specifically affect muscle groups with strong CM connections. This specific pattern could help to refine clinical and electrophysiological ALS diagnostic criteria and complement prospective clinicopathological correlation studies.
- amyotrophic lateral sclerosis
- corticospinal tract
- monosynaptic transmission
- neuropathological staging
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Contributors ACL planned the study, tested patients using the Medical Research Council (MRC) scale, and contributed to writing the original and revised versions of the manuscript as submitted; SE tested patients using the MRC scale; JD and AR retrospectively analysed the records of patients and contributed to the revision of the manuscript; JD and AK performed the statistics; AK contributed figures 2–5; RNL, KDT and HB contributed to writing the original and revised versions of the manuscript as submitted.
Funding This work was funded, in part, by the Virtual Helmholtz Institute for RNA Dysmetabolism in ALS and FTD and the German Research Council (DFG) (LU 336/15-1)
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article.
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