Superconditioning TMS unmasks latent voluntary innervation in MND – A case report

Abstract

Motor neuron disease (MND) includes both ALS and Progressive Muscular Atrophy (PMA) as variants. Abnormalities in brain excitability and upper motor neuron (UMN) function are characteristic of ALS, but by definition are absent in PMA. Transcranial magnetic stimulation (TMS) may be useful in demonstrating UMN pathology, but loss of muscle responsiveness with disease progression limits its usefulness in later stages of MND. We have developed a novel form of TMS comprised of 4 stimulating pulses that can enhance MEPs in target muscles already responding to traditional TMS inputs, in some cases even restoring MEPs in target muscles rendered unresponsive by the disease. An example of restored MEPs in response to this superconditioning TMS pattern (TMSsc) in a person with PMA is described, along with an unexpected finding. Despite a prolonged (> 5 year) history of movement paralysis in his right tibialis anterior (TA), immediately after cessation of TMSsc delivery the subject could now easily contract and relax this muscle; the presence of a latent pathway for voluntary innervation of his right TA was revealed. This modulation of central motor functional connectivity in response to TMSsc suggests a further, clinically-significant benefit of this form of noninvasive brain stimulation beyond its ability to enhance MEPs to traditional TMS inputs.