LAUSR

Introduction Motor unit number estimations methods have been used to quantify the loss of motor units underlying ALS, a deadly neurodegenerative disease. MUNIX relies on surface interference patterns (SIP) recorded during voluntary isometric contractions. In contrast, the recently developed MSCAN techniques is based on threshold tracking and uses natural threshold oscillations of single axons to identify the number of motor units present. MSCAN allows to estimate the composition of the CMAP from single units and allows to simulate the composition of single motor units. Both studies require approximately 5 min per muscle and an optimal CMAP as starting point. Objective Our goal was to show a loss of motor units and a decrease of CMAP in ALS patients over time with MSCAN under realistic medical care conditions. Using MSCAN records and ALSFRS-R, we wanted to show disease progression. Methods MSCAN measurements were performed in 47 ALS patients in up to three muscles in the less affected side (APB, ADM, TA) by threshold-tracking experienced staff. Follow-up measurements were performed after six months in 21 patients. To minimize movement artifacts, limbs were fixed using vacuum cushions. Disease duration, ALSFRS-R, progression rate, ALSFRS-R subscores, diagnostic certainty and clinical stage were extracted from our local database which is an integral part of patient care and reports patient status continuously. Measurements were correlated with model based parameters of ALS progression. Also we calculated ALSFRS-R at the time of the MSCAN measurement taking into account the duration of the disease and D50, which is the number of months after which ALSFRS is reduced to 50% and therefore reflects disease progression. Results MSCAN values and CMAP amplitudes showed a linear correlation in all muscles in base measurement as well as in follow-up measurement. In the follow-up measurements, a decrease compared with base values could be shown in all three muscles. Concerning motor units, this effect could also be detected in the two hand muscles, but not in TA. The quality and stability of the measurements were greatly improved by fixation of the limbs and using bipolar stimulation. MSCAN values did not correlate with total ALSFRS-R, cervical respectively lumbal ALSFRS-subscores nor disease duration in our cohort. A trend was seen in MSCAN units respectively CMAP and calculated ALSFRS and D50. Conclusion MSCAN measurements in clinical routine are feasible and show a reduction of motor units and CMAP in ALS patients over time. The correlation with functional measures was limited, likely due to the focal nature of the measurement. Further longitudinal studies are required to estimate MSCANs value as a prognostic and disease monitoring marker. Acknowledgment This research is supported by BMBF ( Bundesministerium fur Bildung and Forschung ) in the framework of the E-RARE programme (PYRAMID) and JPND (OnWebDUALS) of the European Union.