Abstract
Objective: To determine whether cortical hyperexcitability was more prominent in cognitively impaired amyotrophic lateral sclerosis (ALS) patients.
Methods: Threshold tracking transcranial magnetic stimulation (TMS) was utilised to assess cortical excitability, while cognitive function determined by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Cognitive impairment was defined by ECAS<105. ALS patients, defined by the Awaji criteria, were prospectively recruited. Patients unable to undergo TMS, or in whom TMS indices were compromised by coexistent medical conditions were excluded. Cortical hyperexcitability was defined by reduced short interval intracortical inhibition (SICI) and increased short interval intracortical facilitation (SICF), index of excitability (IE) and motor evoked potential (MEP) amplitude. Student t-test determined differences between groups, while multivariable regression modelling was utilised to assess association between cognitive, clinical and TMS parameters. TMS results were compared to 42 controls.
Results: Cognitive impairment was evident in 36% of the 40 ALS patents (23 males, mean age 62.1 years). Cortical hyperexcitability was more prominent in cognitively impaired patients as indicated by an increase in SICF (ECAS≥105 -15.3±1.7%; ECAS<105 -20.6±1.2%, P<0.01), IE (ECAS ≥105 80.9±7.8; ECAS <105 95.0±4.5, P<0.01) and MEP amplitude (ECAS≥105 28.7±3.3%; ECAS<105 43.1±5.9%, P<0.05). SICF was independently associated with the ECAS score (β=2.410, P<0.05). Reduced SICI was evident in ALS, being more prominent in patients with reduced executive score (ECASexecutive score>33 6.2±1.3%; ECASexecutive score<33 1.5±2.1%, P<0.01).
Conclusion: Cortical hyperexcitability was more prominent in cognitively impaired ALS patients. Given that ECAS is a valid predictor of TDP-43 pathology, the increase in cortical hyperexcitability may be associated with TDP-43 accumulation.
- Received September 6, 2020.
- Accepted in final form January 19, 2021.
- © 2021 American Academy of Neurology
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