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

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Boudewijn T.H.M. Sleutjes (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)
Camiel A. Wijngaarde (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)
H. Stephan Goedee (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)
Louise A.M. Otto (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)
Renske I. Wadman (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)
Inge Cuppen (Department of Neurology and Child Neurology, Brain Center Rudolf Magnus, Wilhelmina's Children Hospital, University Medical Center Utrecht)
Leonard H. van den Berg (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)
W. Ludo van der Pol (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht)

Abstract:
Spinal muscular atrophy (SMA) is a monogenetic neurological disorder that predominantly affects children. SMA presents with a wide range in severity and a high degree of morbidity. A reduced production of the SMN-protein (survival motor neuron) leads to the progressive loss of motor axons causing loss of motor function and muscle strength. The recent introduction of the drug Spinraza (Nusinersen) marked a breakthrough as it showed efficacy in severely affected childhood-onset patients. Most of clinical trials rely on measures of gross motor function. Sensitive outcome measures that can capture subtle, but highly relevant therapeutic effects are therefore highly warranted. Treatments aiming to reduce loss of motor axons require objective tools to quantify such an effect. Therefore, we applied the compound muscle action potential (CMAP) scan, which is a electrophysiological tool that successively activates all motor axons innervating the muscle by increasing transcutaneous stimulus-currents. It captures the contribution of enlarged motor units (MUs; increased muscle fiber number per axon) due to reinnervation by the presence of relative large discontinuities in the scan. The aim of this study was to identify pathophysiological changes of axon loss and reinnervation in SMA using the CMAP scan. Recordings were obtained from 21 patients with SMA (median age 39, range 12 – 67). Stimulus-currents were applied on the left and right median nerve at the wrist and motor responses were recorded from the thenar muscles. The largest discontinuities in the CMAP scan were quantified by means of a novel marker, D50, where a low number is indicative of axon loss and enlarged MUs. The median maximum CMAP amplitude was 8.4 mV (range 0.9 – 14.6 mV) and median D50 was 31 (range 3 – 57). Nine SMA patients with a normal CMAP amplitude (> 3.5 mV) had a reduced D50 (< 25), which is indicative of axon loss and enlarged MUs. These findings suggest that the CMAP scan is a promising tool in detecting pathological changes in SMA, more so than standard maximum CMAP. It is quick and easy to perform, and has the potential to be useful for follow-up studies to monitor treatment efficacy and natural disease course.