Abstract Details

Prospective observational study of 95 definite/clinically suspected NDM participants from six sites (USA, UK, Canada; CINCH consortium) between March 2006-March 2009. Outcomes included standardized symptom interview/physical exam, Short Form-36/Individualized Neuromuscular Quality of Life instruments, electrophysiological short/prolonged exercise tests, manual muscle testing (MMT, average composite 24 muscles), grip strength, and modified get-up-and-go test (GUG).  Standard descriptive statistics and one-way ANOVA were used for comparison.

Comparisons were restricted to confirmed sodium (baseline, year 1, year 2: n=34, 19, 13), chloride (n=32, 26, 18), and myotonic dystrophy type 2 (n=9, 6, 2) mutations.  Muscle stiffness was the most predominant symptom over time (54.7% - 64.7%).   Eyelid myotonia and paradoxical handgrip/eyelid myotonia were more frequent in SCN4A.  Grip strength and combined MMT (average baseline CLCN1 4.49, SCN4A 4.67, DM2 4.36) were stable over time.  Modified GUG showed less improvement between 4 repeated trials at each timepoint in SCN4A (range -0.17 to -0.37 seconds) compared to CLCN1 (-0.98 to -1.42 seconds) but was stable over time. Median short exercise decrement from baseline amplitude at room temperature was 27.22% (range 6.60-45.59) CLCN1 and 6.54% (range -3.69-21.79) SCN4A.  Decrement post-cooling was increased for SCN4A [36.19% (0.66-50.1)]. The mean post short exercise decrement was stable over time, except for SCN4A [baseline to Year 2 decrement difference 16.2% (3.02-29.38)].  Fournier patterns were inconsistent over time. INQoL total score showed higher disease impact for SCN4A and DM2 than CLCN1 with total scores stable over time.

MMT, GUG, and short exercise test decrements were stable over time.  QOL was impacted in the majority of NDMs. Symptomatic therapies may be important for disease altering/symptomatic control.