BACKGROUND AND PURPOSE: The diagnosis of amyotrophic lateral sclerosis (ALS) 
relies on identification of a combination of upper and lower motor neuron signs. 
In order to improve the diagnostic sensitivity for ALS, Awaji criteria were 
developed, in part to better incorporate neurophysiological measures, although 
assessment of upper motor neuron dysfunction remained clinically based. Given 
that cortical hyperexcitability appears to be an early feature in ALS, the 
present study assessed the diagnostic utility of a threshold tracking 
transcranial magnetic stimulation technique as an aid to the research-based 
Awaji criteria in establishing an earlier diagnosis of ALS.
METHODS: Prospective studies were undertaken on a cohort of 82 patients with 
suspected ALS and results were compared with 34 healthy controls.
RESULTS: Short-interval intracortical inhibition (SICI) was significantly 
reduced in ALS patients (P < 0.0001), with a comparable reduction evident in the 
Awaji groups (SICIAWAJI POSSIBLE 1.3% ± 1.3%; SICIAWAJI PROBABLE/DEFINITE 
1.4% ±1.7%). Central motor conduction time was significantly prolonged 
(P < 0.001), whereas the motor evoked potential amplitude (P < 0.05) and 
intracortical facilitation (P < 0.05) were increased. The frequency of 
transcranial magnetic stimulation abnormalities was similar across Awaji 
subgroups, and addition of transcranial magnetic stimulation abnormalities as a 
diagnostic category enabled reclassification of 88% of Awaji possible patients 
to Awaji probable/definite.
CONCLUSIONS: Cortical excitability studies potentially facilitate an earlier 
diagnosis of ALS when combined with clinical and conventional neurophysiological 
findings, albeit in a research setting.