A quantitative measure of handgrip myotonia in non‐dystrophic myotonia

Introduction: Non‐dystrophic myotonia (NDM) is characterized by myotonia without muscle wasting. A standardized quantitative myotonia assessment (QMA) is important for clinical trials. Methods: Myotonia was assessed in 91 individuals enrolled in a natural history study using a commercially available computerized handgrip myometer and automated software. Average peak force and 90% to 5% relaxation times were compared with historical normal controls studied with identical methods. Results: Thirty subjects had chloride channel mutations, 31 had sodium channel mutations, 6 had DM2 mutations, and 24 had no identified mutation. Chloride channel mutations were associated with prolonged first handgrip relaxation times and warm‐up on subsequent handgrips. Sodium channel mutations were associated with prolonged first handgrip relaxation times and paradoxical myotonia or warm‐up, depending on underlying mutations. DM2 subjects had normal relaxation times but decreased peak force. Sample size estimates are provided for clinical trial planning. Conclusion: QMA is an automated, non‐invasive technique for evaluating myotonia in NDM. Muscle Nerve 46: 482–489, 2012

[1]  K. Ricker,et al.  Successful treatment ofparamyotonia congenita (Eulenburg): musclestiffness andweakness prevented bytocainide , 1980 .

[2]  M. Stokes,et al.  Physiological characterisation of the "warm up" effect of activity in patients with myotonic dystrophy. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[3]  M. Zwarts,et al.  Transient paresis in myotonic syndromes. A surface EMG study. , 1989, Brain : a journal of neurology.

[4]  J. Haines,et al.  Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene. , 1990, Science.

[5]  G. Lathrop,et al.  Paramyotonia congenita and hyperkalemic periodic paralysis are linked to the adult muscle sodium channel gene , 1991, Annals of neurology.

[6]  M. Leppert,et al.  Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus. , 1991, American journal of human genetics.

[7]  K. Grzeschik,et al.  The skeletal muscle chloride channel in dominant and recessive human myotonia. , 1992, Science.

[8]  H. Lerche,et al.  Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III‐IV linker. , 1993, The Journal of physiology.

[9]  M. Crackower,et al.  Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita) , 1993, Nature Genetics.

[10]  F. Lehmann-Horn,et al.  A novel SCN4A mutation causing myotonia aggravated by cold and potassium. , 1993, Human molecular genetics.

[11]  R. Moxley,et al.  Myotonia fluctuans. A third type of muscle sodium channel disease. , 1994, Archives of neurology.

[12]  G. Meola,et al.  Quantitative myotonia assessment: an experimental protocol , 2000, Neurological Sciences.

[13]  D. Stegeman,et al.  Propagation disturbance of motor unit action potentials during transient paresis in generalized myotonia: a high-density surface EMG study. , 2001, Brain : a journal of neurology.

[14]  J. Willer,et al.  Electromyography guides toward subgroups of mutations in muscle channelopathies , 2004, Annals of neurology.

[15]  A. Wiegner,et al.  Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1 , 2004, Neurology.

[16]  A. Wiegner,et al.  Quantitative analysis of the “warm‐up” phenomenon in myotonic dystrophy type 1 , 2005, Muscle & nerve.

[17]  E. Colding-Jørgensen.  Phenotypic variability in myotonia congenita , 2005, Muscle & nerve.

[18]  D. Stegeman,et al.  Na+‐K+‐ATPase is not involved in the warming‐up phenomenon in generalized myotonia , 2006, Muscle & nerve.

[19]  S. Pandya,et al.  Computerized hand grip myometry reliably measures myotonia and muscle strength in myotonic dystrophy (DM1) , 2007, Muscle & nerve.

[20]  D. Kullmann,et al.  Chloride channel myotonia: exon 8 hot-spot for dominant-negative interactions. , 2007, Brain : a journal of neurology.

[21]  J. Allum,et al.  Trunk sway analysis to quantify the warm-up phenomenon in myotonia congenita patients , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[22]  G. Drost,et al.  Redefining the clinical phenotypes of non-dystrophic myotonic syndromes , 2009, Journal of Neurology, Neurosurgery, and Psychiatry.

[23]  J. Hogrel.  Quantitative myotonia assessment using force relaxation curve modelling , 2009, Physiological measurement.

[24]  M. Mcdermott,et al.  Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1 , 2010, Neurology.

[25]  S. Cannon,et al.  The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. , 2010, Brain : a journal of neurology.

[26]  R. Moxley,et al.  Evoked myotonia can be “dialed‐up” by increasing stimulus train length in myotonic dystrophy type 1 , 2009, Muscle & nerve.

[27]  W. Groh.  Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1 , 2011, Neurology.

[28]  M. Koltzenburg,et al.  Refined exercise testing can aid dna‐based diagnosis in muscle channelopathies , 2011, Annals of neurology.