Triple-Timed Up-and-Go Test Effective in Assessing LEMS Severity, Trial Analysis Shows

The Triple-Timed Up-and-Go (3TUG) test is a rapid, non-invasive, reliable, and reproducible measurement for assessing muscle weakness in people with Lambert-Eaton myasthenic syndrome (LEMS), analysis of the Phase 2 DAPPER trial shows.

The study, “Validation of the Triple Timed Up-and-Go Test in Lambert-Eaton Myasthenia,” was published in the journal Muscle and Nerve.

There are no validated, practical, and quantitative ways of evaluating the severity of LEMS. Electrodiagnostic studies, which assess the function of muscle and nerves, are time-consuming, and in some cases can only be carried out in specialized treatment centers. The Quantitative Myasthenia Gravis Score — a 39-point scale that measures disease severity — does not include assessments of key causes of LEMS’ related disabilities, including weakness of lower extremities and reduced mobility.

The Timed Up-and-Go (TUG) test provides a way to measure mobility. The test measures the time it takes for an individual to rise from the seat of a straight-backed armchair, walk three meters at normal speed, turn, walk back to the chair, and sit down. It has already been shown to be a successful assessment, mainly in elderly individuals with Parkinson’s disease and impaired cognition.

A variation of TUG, the Triple Timed Up-and-Go (3TUG) test involves three repetitions of the measurement circuit, without rest. The 3TUG test time is the average of these three repetitions. This assessment measures weakness and fatigue of the lower extremities, which are symptoms characteristic of LEMS. Further, the 3TUG test does not require specialized equipment or technical training.

While the 3TUG test has shown promising results in patients with different neuromuscular diseases, it had not previously been fully validated in LEMS.

To assess its usefulness, researchers from Duke University analyzed data from the Phase 2 DAPPER (NCT01511978) trial. That study included 32 adults with LEMS who had been taking Ruzurgi for at least three months before enrolling. Participants were randomly selected to continue treatment with Ruzurgi, as 30 to 100 mg daily, divided into at least three doses, or to stop Ruzurgi and switch to a placebo.

In the trial, the outcomes of the treatment were mainly assessed using the 3TUG test.

Now, the researchers first assessed the reproducibility of the 3TUG test — or its ability to give the same result in a retest. The results showed the test’s reproducibility was good, with only 20% or less variability seen in test times recorded for the same individual on two consecutive days.

Further, the 3TUG test times significantly correlated with patients’ scores on the Lower Extremity Function scale, a questionnaire containing 20 queries concerning an individual’s ability to perform everyday tasks. The correlations held both for patients treated with Ruzurgi and those who had discontinued treatment.

The results of the 3TUG test also significantly correlated with patients’ scores on another assessment scale, the Weakness Self Assessment Scale. This scale includes 7 categories, ranging from a -3 representing “Much Much Weaker,” to a +3, which represents “Much Much Stronger.” Worsening of three or more points in the Weakness Self Assessment Scale corresponded to an increase of over of 73.6% of the 3TUG time.

The decline in the 3TUG test also was in agreement with the worsening seen by investigators.

“Together, these results indicate that the 3TUG is responsive to patient- and clinician-reported changes in disease severity. This offers an advantage over electrophysiologic measures because it can be performed without special equipment and technical training,” the researchers said.

“The 3TUG is a practical, validated outcome measure for clinical assessment of LEM patients that is suitable for use in the clinic, as well as in clinical trials,” the study concluded.