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. 2021 Sep 13:12:20406223211044072.
doi: 10.1177/20406223211044072. eCollection 2021.

The ipsilateral silent period: an early diagnostic marker of callosal disconnection in ALS

Annemarie Hübers  1 , Jan Kassubek  2 , Hans-Peter Müller  2 , Nicolas Broc  3 , Jens Dreyhaupt  4 , Albert C Ludolph  2
Affiliations

The ipsilateral silent period: an early diagnostic marker of callosal disconnection in ALS

Annemarie Hübers et al. Ther Adv Chronic Dis. .

Abstract

Introduction: Imaging studies showed affection of the corpus callosum (CC) in amyotrophic lateral sclerosis (ALS). Here, we sought to determine whether these structural alterations reflect on the functional level, using transcranial magnetic stimulation (TMS).

Methods: In 31 ALS patients and 12 controls, we studied mirror movements (MM) and transcallosal inhibition (TI) using TMS. Structural integrity of transcallosal fibres was assessed using diffusion tensor imaging.

Results: TI was pathologic in 25 patients (81%), 22 (71%) showed MM. Loss of TI was observed in very early stages (disease duration <4 months). No correlation was found between TI/MM and fractional anisotropy of transcallosal fibres.

Discussion: These results substantiate the body of evidence towards a functional involvement of the CC in early ALS beyond microstructural alterations.

Significance: TI may become a useful early diagnostic marker in ALS, even before descending tracts are affected. Diagnostic delay in ALS is high, often preventing patients from gaining access to therapeutic trials, and sensitive diagnostic tools are urgently needed. Our findings also provide insights into the pathophysiology of ALS, potentially supporting the so-called 'top-down' hypothesis, that is, corticoefferent (intracortical/corticospinal) propagation. Callosal affection in early stages might represent the 'missing link' to explain corticocortical disease-spreading.

Keywords: amyotrophic lateral sclerosis; corpus callosum; mirror movements; transcranial magnetic stimulation.

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Conflict of interest statement

Conflict of interest statement: Jan Kassubek is an Associate Editor of Therapeutic Advances in Chronic Disease and an author of this paper, therefore, the peer review process was managed by alternative members of the Board and the submitting Editor had no involvement in the decision-making process. All other authors declared no potential conflicts of interest with respect to the research, authorship and / or publication of this article.

Figures

Figure 1.
Figure 1.
Motor potentials evoked in the left APB (upper row) and surface EMG of the right APB (lower row) during maximal voluntary contraction (averaged EMG of 10 trials) of a control (a) and an ALS patient (b). Note the complete loss of iSP (lower row) in the ALS patient, while present and within normal ranges regarding onset latency, depth and duration in the control. ALS, amyotrophic lateral sclerosis; APB, abductor pollicis brevis; EMG, electromyogram; iSP, ipsilateral silent period.
Figure 2.
Figure 2.
WBSS of fractional anisotropy maps of 19 ALS patients versus 19 controls. Significant alterations were detected along the corticospinal tracts. ALS, amyotrophic lateral sclerosis; FDR, false discovery rate.
See this image and copyright information in PMC

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