Diagnostic utility of cortical excitability studies in amyotrophic lateral sclerosis

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.

Prospective studies were undertaken on a cohort of 82 patients with suspected ALS and results were compared with 34 healthy controls.

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.

Cortical excitability studies potentially facilitate an earlier diagnosis of ALS when combined with clinical and conventional neurophysiological findings, albeit in a research setting.