Transcranial magnetic stimulation identifies upper motor neuron involvement in motor neuron disease

Objective: To evaluate the sensitivity of transcranial magnetic stimulation (TMS) to identify upper motor neuron involvement in patients with motor ne uron disease. Background: Diagnosis of ALS depends on upper and lower motor neuron involvement. Lower motor neuron involvement may be documented with electromyography, whereas definite evidence of upper motor neuron involveme nt may be elusive. A sensitive, noninvasive test of upper motor neuron func tion would be useful. Methods: TMS and clinical assessment in 121 patients with motor neuron disease. Results: TMS revealed evidence of upper motor ne uron dysfunction in 84 of 121 (69%) patients, including 30 of 40 (75%) pati ents with only probable upper motor neuron signs and unsuspected upper moto r neuron involvement in 6 of 22 (27%) patients who had purely lower motor n euron syndromes clinically. In selected cases, upper motor neuron involveme nt identified with TMS was verified in postmortem examination. Increased mo tor evoked potential threshold was the abnormality observed most frequently and was only weakly related to peripheral compound muscle action potential amplitude. In a subset of 12 patients reexamined after 11 +/- 6 months, TM S she-wed progression of abnormalities, including progressive inexcitabilit y of central motor pathways and loss of the normal inhibitory cortical stim ulation silent period. Conclusions: TMS provides a sensitive means for the assessment and monitoring of excitatory and inhibitory upper motor neuron f unction in motor neuron disease.