Test-retest agreement and reliability of the Six Spot Step Test in persons with multiple sclerosis.

BACKGROUND: The Six Spot Step Test (SSST) extends traditional walking outcomes in persons with multiple sclerosis (PwMS) by further challenging components of coordination and balance. Nonetheless, the test-retest agreement of the SSST has not been investigated. OBJECTIVE: To determine the within-day, day-to-day, and inter-rater agreement and reliability of the SSST in PwMS. A secondary aim was to investigate the validity of handheld timing. METHODS: A total of 38 PwMS with an Expanded Disability Status Scale (EDSS) <6.5 completed two SSSTs with a 5-minute break in-between. After 2 days, this procedure was repeated. Bland-Altman analysis was performed to determine the 95% Limits of Agreement (LOA) and Intraclass Correlation Coefficient (ICC) was calculated. In a subgroup of 18 PwMS, the SSSTs were video-recorded and timed by a second investigator. RESULTS: The relative LOA within and between days were ±15% and ±19%, while ICC were 0.987 and 0.983, respectively. A minor learning effect was found over four tests. The handheld timing error was ±0.5 seconds when compared to video-based timing. CONCLUSION: The SSST has an acceptable within- and between-day agreement and reliability. For interventional purposes, a change of >19% can be regarded as a real change. Valid timing can be performed by a handheld stopwatch.

The role of Trypanosoma brucei MRPA in melarsoprol susceptibility.

We previously showed that over-expression of Trypanosoma brucei MRPA, a member of the multidrug resistance protein family in T. brucei, reproducibly resulted in resistance to the anti-trypanosomal drug melarsoprol in vitro. MRPA is predicted to mediate efflux of melarsoprol as a conjugate with trypanothione, a glutathione-spermidine conjugate which is the major small thiol in trypanosomes. Here, we show that depletion of MRPA by RNA interference resulted in moderate hypersensitivity to both melarsoprol and melarsen oxide. Over-expression of MRPA alone is not sufficient to cause melarsoprol resistance in vivo, although it is sufficient in vitro. This discrepancy is not an effect of drug metabolism since over-expression of MRPA alone conferred resistance to melarsoprol and its principle metabolite, melarsen oxide, in vitro. Over-expression of MRPA was not detected in four melarsoprol-resistant trypanosome isolates from sleeping sickness patients.