Correlating EMG exercise tests with genotype International Conference on the Nondystrophic Myotonias Marianne Arzel-Hézode, Emmanuel Fournier Centre de référence des Canalopathies Musculaires Hôpital La Salpêtrière, Paris, France

Muscle channelopathies Patients with EMG and genetic diagnose : Muscle channelopathies Patients with EMG and genetic diagnose : N=171 (La Salpêtrière, 1996-2007) Myotonic syndromes N = 104 Myotonia CLCN1 (A313T, P480L…) 33 Paramyotonia SCN4A (T1313M, R1448C/H/G, Q270K…) 40 SCM («PAM ») SCN4A (G1306A/V, V445M, A715T, S804N…) 31 Periodic paralysis N = 67 HyperPP SCN4A (T704M, R675G, I693T…) 25 HypoPP-1 CACNLA1 (R528H, R1239H) 24 HypoPP-2 SCN4A (R672G/H, R1135H…) 6 Andersen (ATS) KCNJ2 (C54F, T75M, C154F/Y, T309I…) 12

Electrophysiological abnormalities triggered by pioneer tests CMAP amplitude decreases were observed : during 10 Hz repetitive nerve stimulation in myotonic syndromes Lambert et al. 1952, Bastron 1960, Ricker et al. 1973, Brown 1974, Aminoff et al. 1977 after a single short exercise test in myotonic syndromes Streib et al. 1982, Streib 1987 after a long exercise test in periodic paralyses Mc Manis et al. 1986, Kuntzer et al. 2000 MU1 MU2 Supramaximal Nerve stimulation CMAP Interpretation CMAP amplitude correlates with the number of functional muscle fibers Its decrease is an index of muscle weakness experienced after exercise Exercise tests = provocative tests

1st EMG protocol (1996, revised 2000) Long exercise test Right hand (ulnar - ADM) Exercise lasting 5 minutes (respecting regular brief rests) Recording every 5 minutes during 40-45 minutes post-exercise rest II Repeated short exercise test Left hand (ulnar - ADM) 3 exercises of 10 seconds with 1 minute between each trial Recording every 10 seconds for 50 seconds after each exercise Ann Neurol 2004 Patients N = 51 Chlore Myotonia (MC) 6 Paramyotonia (PC) 16 Sodium Myotonia (SCM) 8 Sodium HyperPP 6 Sodium HypoPP-2 2 Calcium HypoPP-1 13 Control Subjects N = 41 III Search for myotonic discharges with needle EMG Deltoid, extensor digitorum communis, 1st interosseus dorsalis, tibialis anterior

1st EMG protocol

Repeated short exercise test Chloride Myotonia - 61 % - 45 % - 20 % « Warm-up » phenomenon Type II Post-exercise myotonic potentials (PEMP) Sodium Paramyotonia - 48 % - 64 % Aggravation with exercise repetition Stiffness-weakness continuum Type I

Five main EMG patterns Fournier et al. Ann Neurol 2004

for distinguishing myotonic syndromes (2003) 2nd EMG protocol for distinguishing myotonic syndromes (2003) I Repeated short exercise test Right hand (ulnar -ADM) 3 exercises of 10 s with 50 s rest intervals II Cooling test Left hand (ulnar -ADM) Ice bag for 7 minutes Repeated short exercise test at cold 3 exercises of 10 s with 50 s rest intervals Ann Neurol 2006 Patients N = 61 Chlore Myotonia 18 Paramyotonia (PC) 22 Sodium Myotonia (SCM) 14 DM1/DM2 7 Control Subjects N = 31 III Search for myotonic discharges Needle EMG of deltoid, EDC, 1st IOD, tibialis anterior Total exam lasts 20 minutes

2nd EMG protocol for distinguishing myotonic syndromes

Improvement of EMG distinctions with cold - 82 % - 90 % - 93 % Worsening of the abnormalities observed at room temperature Pattern changes

EMG guides toward myotonic syndrome genotypes 80 % SCN4A 100 % SCN4A 86 % 85 % 60 % 14 % 15 % 20 % 20 % Ann Neurol 2006

EMG Protocols’ Objectives Diagnosis Disclose functional abnormalities by mimicking provocative circumstances Explain symptoms (electrical response changes as index ) Determine differential diagnosis of weakness episodes And more : distinguish closer clinical phenotypes Guide molecular diagnosis Isolate physiopathological mechanisms Look for therapeutical advances