Early diagnosis of amyotrophic lateral sclerosis (ALS) may be possible with short-interval intracortical inhibition by threshold tracking (T-SICI) with transcranial magnetic stimulation according to a study that compared it with conventional amplitude measurements (A-SICI).

Australian and international researchers investigated the clinical diagnostic sensitivity and specificity of T-SICI using a new parallel method and compared it with A-SICI in a cohort of 104 patients referred suspected ALS, in whom the diagnoses were subsequently confirmed or excluded by clinical follow-up.

There were 62 patients who had disease progression after follow up of 2.5 years and were diagnosed with motor neuron disease (MND), while 42 patients were classified as ALS mimics.

All patients had T-SICI and A-SICI recorded in first dorsal interosseus (index test) and the results were compared with recordings from 53 age-matched healthy controls. The reference standard was the Awaji criteria

The results showed that both threshold tracking and conventional transcranial magnetic stimulation had good sensitivity and specificity for discriminating MND patients from patient controls. Patients with MND had significantly reduced T-SICI and A-SICI compared with the healthy and patient control groups, with areas under ROC curves of 0.762 and 0.810 respectively at 1-3.5ms.

The conventional A-SICI method produced less variable measurements in all groups than the T-SICI method and it provided slightly better discrimination between the MND patients and patient controls. Paradoxically, the T-SICI was most abnormal before upper motor neuron (UMN) signs had developed.

This unusual finding provided clues to the pathophysiology of ALS, said the study investigators, which inlcuded Dr James Howells of the Universty of Sydney. They said the most likely explanation was that the cortical motoneurones experiencing most facilitation progressively degenerated, consistent with an excitotoxic mechanism, while those experiencing inhibition survive.

The changes in A-SICI were less pronounced since the stronger stimuli used sample a larger proportion of motoneurones, they noted.

The implication was that both methods may be good markers of ALS, with the T-SICI having potential for diagnosing sub-clinical disease.

“We have found that both A-SICI and T-SICI are sensitive early indicators of UMN dysfunction in patients referred for suspicion of ALS, with T-SICI most abnormal before UMN signs have developed,” they concluded.

“We therefore strongly support arguments that SICI should be accepted as an aid to the early diagnosis of ALS. On the other hand, since T-SICI becomes more normal as signs of disease progression increase, it may not be suitable for monitoring potential ALS treatments.”

The findings are published in the European Journal of Neurology.