Treatment of myotonia congenita with retigabine in mice.

Patients with myotonia congenita suffer from muscle stiffness caused by muscle hyperexcitability. Although loss-of-function mutations in the ClC-1 muscle chloride channel have been known for 25 years to cause myotonia congenita, this discovery has led to little progress on development of therapy. Currently, treatment is primarily focused on reducing hyperexcitability by blocking Na+ current. However, other approaches such as increasing K+ currents might also be effective. For example, the K+ channel activator retigabine, which opens KCNQ channels, is effective in treating epilepsy because it causes hyperpolarization of the resting membrane potential in neurons. In this study, we found that retigabine greatly reduced the duration of myotonia in vitro. Detailed study of its mechanism of action revealed that retigabine had no effect on any of the traditional measures of muscle excitability such as resting potential, input resistance or the properties of single action potentials. Instead it appears to shorten myotonia by activating K+ current during trains of action potentials. Retigabine also greatly reduced the severity of myotonia in vivo, which was measured using a muscle force transducer. Despite its efficacy in vivo, retigabine did not improve motor performance of mice with myotonia congenita. There are a number of potential explanations for the lack of motor improvement in vivo including central nervous system side effects. Nonetheless, the striking effectiveness of retigabine on muscle itself suggests that activating potassium currents is an effective method to treat disorders of muscle hyperexcitability.

Quantification of mobility impairment and self-assessment of stiffness in patients with myotonia congenita by the physiotherapist.

We investigated test-retest reliability and responsiveness in two functional measuring instruments, Timed Up&Go (TUG) and Timed-Stands Test (TST), and in three self-assessment scales, Visual Analogue Scale (VAS), Borg's Category-Ratio Scale (BorgCR10) and Myotonia Behaviour Scale (MBS) when quantifying myotonic stiffness and mobility impairment. These methods were used in the assessment of treatment efficacy of mexiletine. Six male patients with myotonia congenita followed a standardised protocol with time scoring and rest on two occasions, with and without mexiletine. Time scoring of TUG and TST and self-assessments of stiffness were performed. A 14-day stiffness diary was used at home. Timed Up&Go and TST showed very good test-retest agreement (ICC=0.87-0.95) and significant to change (P=0.005 and 0.001, respectively). All self-assessment scales revealed excellent responsiveness and good test-retest reliability. The measurement instruments possess great capacity to detect functional impairment in the myotonia congenita patient group, and sensibility to identify true changes due to treatment. When considering the results, three instruments are favoured; Timed Up&Go and BorgCR10 for short, and MBS for long-term evaluations.

Myotonia congenita: quantitation of different aspects of motor performance.

In order to quantitatively assess the motor performance characteristics of 14 patients with congenital myotonia, the reaction time, speed of movement, synergy of different muscle groups and accuracy were measured. The Human Performance Measurement/Basic Elements of Performance device was used for recordings. Warned simple and choice reaction times (SRT, CRT) were significantly longer in the myotonic patients than in the controls. SRTs, consisting of one constant visual stimulus followed by a single movement response of the upper extremities (patients vs. controls) were 218 +/- 48 ms (mean +/- SD) and 172 +/- 12 (p = 0.0038). In the lower extremities the corresponding results were 293 +/- 46 and 239 +/- 24 (p = 0.0018). 1-CRTs, consisting of the upper extremities response to one randomized light signal (patients vs. controls) were 265 +/- 45 and 218 +/- 26 (p = 0.0069), and those of the lower extremities 337 +/- 73 and 279 +/- 39 (p = 0.0107), respectively. 2-CRTs, consisting of two possible visual stimuli in randomized order followed by a movement response of the upper extremities (patients vs. controls), were 308 +/- 54 and 249 +/- 33 (p = 0.0018), and those of the lower extremities 387 /+- 53 and 323 /+- 46 (p = 0.0028), respectively. We did not find any significant difference between the patient and the control groups in speed of movement, synergy of different muscle groups or accuracy. Nor was any significant correlation between the motor performance disability and the disease severity found.

Intellectual functions and personality in subjects with noncongenital myotonic muscular dystrophy.

Mental retardation and personality disorders are commonly described among the symptoms of myotonic dystrophy. Nevertheless, this tendency is not supported by systematic studies performed on large samples, whose results are controversial. We studied the cognitive functions and personalities of a group of 28 patients, in whom myotonic dystrophy had commenced in juvenile or adult life. The severity of the disease was variable, but all subjects were self-sufficient. Only 7.1% of subjects showed low intelligence with deterioration of perceptual-motor functions. This was not correlated with the severity of their disease. Women had a substantially lower mean Wechsler-Bellevue score than men. The personality function study of the entire group showed no change of psychiatric relevance but did present a depressive attitude with marked somatic concern and difficulties in establishing relationships in social life.

Inside-of-the-Body test drawings performed by patients with neuromuscular diseases: a preliminary report.

Inside-of-the-Body test drawings were obtained from 50 individuals with various neuromuscular diseases. A mean of 18.0 +/- 5.1 body parts were identified in the drawings. Diseased body structures were emphasized by most patients; for example, thymus was only drawn by individuals with myasthenia gravis, while muscle was only identified by individuals with polymyositis. In contrast, drawings by individuals with neuropathic atrophy omitted the atrophic extremities.