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Sarcolemmal excitability attributes of the myotonic dystrophies as assessed by muscle velocity recovery cycles (mvrcs)
  1. Robert Boland-Freitas1,2,
  2. James Howells3,
  3. James Lee1,
  4. Christina Liang1,
  5. Alastair Corbett4,
  6. Garth Nicholson5,
  7. Karl Ng1,3
  1. 1Department of Neurology and Neurophysiology, Royal North Shore Hospital, St Leonards, NSW, Australia
  2. 2Neurology Department, Blacktown Hospital, Blacktown, NSW, Australia
  3. 3Sydney Medical School – K25, Camperdown, NSW, Australia
  4. 4Department of Neurology, Concord Hospital, Concord, NSW, Australia
  5. 5Department of Molecular Medicine, Concord Hospital, Concord, NSW, Australia

Abstract

Objectives Myotonic dystrophy is the most prevalent form of muscular dystrophy in adults. Two distinct subtypes exist; myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2). Muscle velocity recovery cycle (MVRCs) assessment represents a new automated technique whereby muscle membrane polarisation properties can be quantitated in vivo. The study aim was to characterise the excitability attributes of DM1 and DM2 comparing with that of normal control subjects and the results of a recently published myotonic dystrophy cohort using the same technique1.

Methods Recordings were made from the tibialis anterior muscle of 20 DM1 patients and 4 DM2 patients using QTracS/P excitability assessment software. DM1 patients were classed according to the severity of manually assessed muscle weakness using the Muscle Impairment Rating Scale (MIRS), MIRS grade 3 and above (MIRS3+) denoting the presence of limb muscle weakness. MVRCs and frequency ramp sections of testing were included in analysis, compared to recordings from 30 normal control subjects.

Results Nineteen DM1 patients (11 MIRS3+) and 4 DM2 patients were incorporated in the final analysis. In the MIRS3+ DM1 and DM2 patients, 5XRSN (extra residual supernormality after 5 conditioning stimuli) was significantly increased in comparison to normal controls. Only MIRS3+ DM1 patients exhibited significant changes in muscle relative refractory period, early supernormality, as well as significantly more marked peak amplitude decrements during the frequency ramp (p<0.0001), consistent with depolarisation of the resting muscle membrane potential.

Conclusions Despite similarities in some respects, DM1 and DM2 exhibit differences in sarcolemmal excitability likely due to impairments of in Na+/K+ ATPase function seen in more advanced stages of DM1 only. This is likely to be as a result of progressive DMPK deficiency in DM1, with possible implications for emerging therapies for DM1 that knock down the transcription of the DMPK gene.

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