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Session: Neuromuscular – upper extremities
Session starts: Friday 25 January, 10:30
Presentation starts: 11:15
Room: Lecture room 535

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Boudewijn T.H.M. Sleutjes (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)
Ernest Boskovic (Department of Medical Technology and Clinical Physics, University Medical Center Utrecht, The Netherlands)
Leonard J. van Schelven (Department of Medical Technology and Clinical Physics, University Medical Center Utrecht, The Netherlands)
Leonard H. van den Berg (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)
Hessel Franssen (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)

Abstract:
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the progressive loss of motor neurons that innervate muscles leading to muscle weakness and, ultimately, death. A major challenge is to identify the pathophysiological mechanisms that contribute to the disease, and find sensitive markers to measure treatment efficacy. A promising target for disease-modifying treatment involves ion channels of which their dysfunction has been associated with motor neuron degeneration in ALS. Studying ionic processes in motor neurons (= nerve cells) however often remains limited to basic cellular or animal studies while sensitive markers of their dysfunction in humans are strongly needed. Therefore, we recently developed a new tool that enables recording single motor neuron ion channel functioning in humans directly [1]. Using multichannel surface-EMG, we identified single motor unit potentials (MUPs), generated by the muscle fibers innervated by single motor neurons. Excitability testing applied on single MUPs allowed assessment of their ion channel function. The aim of this study is to show the current state of this new tool and practical aspects for further development. With multichannel surface-EMG a 9-by-14 multi-electrode array is placed on the skin overlying the thenar muscles. This records 126 surface-EMG signals, providing spatial information which aids single MUP detection. In 10 healthy subjects, we have successfully obtained excitability measures from 14 single MUPs. From the 126 EMG signals, one EMG signal, most selective for a single motor neuron, was transferred to the excitability testing setup. To ensure that changes in single MUPs can be ascribed to pathophysiological changes, further implementation requires assessing the physiological variability of single MUPs, and standardization of the set-up to allow their redetection in subsequent sessions. This promising tool has the potential to identify new targets for treatment when monitoring the disease process in single motor neurons. It may further be used to determine biological target engagement of candidate drugs on single motor neurons in patients directly. This will bridge the gap between cellular based studies and large clinical trials accelerating the development of new treatments. [1] BTHM Sleutjes, J Drenthen, E Boskovic, LJ van Schelven, MO Kovalchuk, PGE Lumens, LH van den Berg, H Franssen. Excitability tests using high-density surface-EMG: A novel approach to studying single motor units, Clinical Neurophysiology, 129 (8): 1634 – 1641, 2018