Pathophysiological associations of transcallosal dysfunction in ALS

Abstract

Aim Involvement of the corpus callosum has been identified as a feature of amyotrophic lateral sclerosis (ALS), particularly through neuropathological studies. The aim of the present study was to determine whether alteration in transcallosal function contributed to the development of ALS, disease progression and thereby functional disability. Methods Transcallosal function and motor cortex excitability were assessed in 17 ALS patients with results compared to healthy controls. Transcallosal inhibition (interstimulus intervals (ISI) of 8–40 ms), short interval intracortical facilitation (SICF) and inhibition (SICI) were assessed in both cerebral hemispheres. Patients were staged utilising clinical and neurophysiological staging assessments. Results In ALS, there was prominent reduction of transcallosal inhibition (TI) when recorded from the primary and secondary motor cortices compared to controls (F = 23.255, p < 0.001). This reduction of TI was accompanied by features indicative of cortical hyperexcitability, including reduction of SICI and increase in SICF. There was a significant correlation between the reduction in TI and the rate of disease progression (R = −0.825, p < 0.001) and reduction in muscle strength (R = 0.54, p = 0.031). Conclusion The present study has established that dysfunction of transcallosal circuits was an important pathophysiological mechanism in ALS, correlating with greater disability and a faster rate of disease progression. Therapies aimed at restoring the function of transcallosal circuits may be considered for therapeutic approaches in ALS.

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

“…No correlation between callosal function and diffusion imaging measures could be observed. These results are in line with previous studies 6 ,11, 12 and suggest that functional disturbance might precede detectable microstructural abnormalities. Of note, patients in our cohort showed no alterations of the CST (i.e.…”

“…Reduction of functional TI has been reported in ALS patients, but the electrophysiological findings seem not to be associated with a decrease of fractional anisotropy (FA) in the motor region of the CC. 11 , 12 …”

Diagnostics of Amyotrophic Lateral Sclerosis: Up to Date

“…It has been recently published that short- and long-latency afferent inhibitions after TMS were both impaired in ALS, probably unrelated to increased cortical excitability or cognitive dysfunction [ 75 ]. Dysfunction of transcallosal circuits using TMS has been observed as an important pathophysiological mechanism in ALS, correlating with greater disability and a faster rate of disease progression [ 76 ].…”

Utility of Transcranial Magnetic Simulation in Studying Upper Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis

“…Reduction of CSP duration has been noted in sporadic and familial ALS cohorts, being most prominent in early disease stages [ 34 , 35 , 36 , 37 , 43 , 44 ]. Abnormalities of ipsilateral CSP have also been reported as an early feature in ALS, signifying loss of transcallosal function [ 44 , 45 ]. Disinhibition at a cortical level, due to degeneration or dysfunction of cortical inhibitory interneurons, appears to underlie the reduction of CSP duration in ALS [ 45 ].…”

“…Abnormalities of ipsilateral CSP have also been reported as an early feature in ALS, signifying loss of transcallosal function [ 44 , 45 ]. Disinhibition at a cortical level, due to degeneration or dysfunction of cortical inhibitory interneurons, appears to underlie the reduction of CSP duration in ALS [ 45 ].…”