Novel Technique Distinguishes Between ALS, Mimic Disorders

Threshold-tracking transcranial magnetic stimulation could be a useful diagnostic technique in the clinical setting.

WASHINGTON — A threshold-tracking transcranial magnetic stimulation technique was shown to reliably distinguish between amyotrophic lateral sclerosis and mimic disorders during early stages of the disease process, suggesting it may serve as a useful diagnostic technique in the clinical setting.

Physicians using current neurologic criteria are limited with upper motor neuron findings, since they have to rely on clinical examination, according to Nimeshan Geevasinga, MBBS, of the University of Sydney, Australia.

“And when we do that, there is a significant delay in diagnosis,” he said in an interview. “So we assessed whether we could employ a novel neurophysiological tool to try to diagnose patients [with ALS] earlier and therefore start clinical trials at an earlier stage.”

Geevasinga and colleagues conducted a prospective study at three neuromuscular centers in Sydney. The findings were presented at the 2015 American Academy of Neurology Annual Meeting.

Patients were recruited between Jan. 1, 2010 and Jan. 3, 2014 and included in the study if they had definite, probable or possible amyotrophic lateral sclerosis (ALS) as defined by the Awaji criteria (n=209), or neuromuscular disorders mimicking ALS (n=69).

In all, 333 patients (61.9% men; mean age, 57.6 years) were enrolled and underwent threshold-tracking transcranial magnetic stimulation (TMS) at recruitment.

Geevasinga and colleagues defined the primary outcome as the diagnostic utility of TMS in distinguishing ALS from non-ALS mimic neuromuscular disorders (NALS).

Mean time from TMS assessment and progression to an ALS diagnosis — defined as Awaji definite/probable ALS — was 15.8 months.

According to data, the threshold-tracking TMS technique reliably differentiated between ALS and NALS, with an area under curve of 0.80 (95% CI, 0.75-0.85), sensitivity of 73.08% (95% CI, 66.51-78.98) and specificity of 82.35% (95% CI, 71.20-90.53).

The number needed to test in order to diagnose one extra case of ALS was 1.8 (95% CI, 1.4-2.7). About 70% of ALS patients categorized as Awaji possible (“not meeting criteria”) had TMS abnormalities.

“Potentially, if we had used this technology at [an earlier] stage, we could have upgraded about 34% of patients from a possible diagnosis, whereby they are ineligible for trials, to a probable or definite criteria,” Geevasinga said.

Going forward, he noted that given the interest in ALS trials that try to find a better therapy for patients, there is the potential to use this technique not only in diagnosis, but also as a biomarker and a tool to elucidate where the underlying problem of ALS starts — the central or peripheral nervous system.

“The fact that we can see these changes so early is promising and warrants further investigation to see whether we can use it on a global scale,” Geevasinga said.


  1. Geevasinga N et al. Abstract I8-5C. Presented at: American Academy of Neurology Annual Meeting 2015; April 18-25, 2015: Washington, D.C.