Non-dystrophic myotonia: prospective study of objective and patient reported outcomes
Non-dystrophic myotonia: prospective study of objective and patient reported outcomes
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DOI：
10.1093/brain/awt133
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发表时间：
2013-07-01
期刊：
影响因子：
14.5
通讯作者：
Barohn, Richard J.
中科院分区：
文献类型：
--
作者：
Trivedi, Jaya R.;Bundy, Brian;Barohn, Richard J.
非营养不良性肌强直是由骨骼肌氯离子和钠离子通道突变引起的罕见疾病，疾病之间具有相当大的表型重叠。很少有前瞻性研究评估大量患者肌强直症状和体征的敏感性。我们对 2006 年 3 月至 2009 年 3 月期间从美国、英国和加拿大的 6 个地点招募的 95 名患有明确或临床疑似非营养不良性肌强直的参与者进行了一项前瞻性观察研究。我们使用了 NIH 资助的罕见疾病临床研究网络提供的通用基础设施和数据元素。结果包括标准化症状访谈和体检； Short Form-36 和个体化神经肌肉生活质量仪器；电生理短期和长期运动测试；手动肌肉测试；以及修改后的起立运行测试。 32 名参与者患有氯离子通道突变，34 名参与者患有钠通道突变，9 名参与者患有 2 型强直性肌营养不良，1 名参与者患有 1 型强直性肌营养不良，17 名参与者没有发现突变。表型比较仅限于钠通道突变、氯通道突变和 2 型强直性肌营养不良的患者。总体而言，肌肉僵硬是最突出的症状，66.7% 至 100% 的参与者出现这种症状。与氯离子通道突变相比，钠突变的参与者出现僵硬的年龄较早（5岁对10岁），频繁出现闭眼肌强直（73.5%对25%），个体化神经肌肉生活质量总结评分受损更多（20.0对9.44），以及反常闭眼肌强直（50%对0%）。四分之三的参与者出现握力肌强直，其中 75% 的氯通道突变出现肌强直，35.3% 的钠通道突变出现肌强直。短期运动测试显示，59.3% 的氯离子通道参与者的复合肌肉动作电位振幅降低了 510%，而钠通道参与者的复合肌肉动作电位振幅为 27.6%，而钠通道突变后冷却后则增加至 57.6%。在对临床和电肌强直患者的评估中，尽管有相当大的表型重叠，但闭眼肌强直、反常性肌强直的存在以及冷却后短期运动试验敏感性的增加表明钠通道突变。无论潜在的突变如何，旨在测量僵硬或僵硬的电生理相关性的结果可能对未来的临床试验有用，并且包括患者报告的僵硬、评估肌强直的床旁操作、肌肉特定的生活质量仪器和短期运动测试。
Non-dystrophic myotonias are rare diseases caused by mutations in skeletal muscle chloride and sodium ion channels with considerable phenotypic overlap between diseases. Few prospective studies have evaluated the sensitivity of symptoms and signs of myotonia in a large cohort of patients. We performed a prospective observational study of 95 participants with definite or clinically suspected non-dystrophic myotonia recruited from six sites in the USA, UK and Canada between March 2006 and March 2009. We used the common infrastructure and data elements provided by the NIH-funded Rare Disease Clinical Research Network. Outcomes included a standardized symptom interview and physical exam; the Short Form-36 and the Individualized Neuromuscular Quality of Life instruments; electrophysiological short and prolonged exercise tests; manual muscle testing; and a modified get-up-and-go test. Thirty-two participants had chloride channel mutations, 34 had sodium channel mutations, nine had myotonic dystrophy type 2, one had myotonic dystrophy type 1, and 17 had no identified mutation. Phenotype comparisons were restricted to those with sodium channel mutations, chloride channel mutations, and myotonic dystrophy type 2. Muscle stiffness was the most prominent symptom overall, seen in 66.7% to 100% of participants. In comparison with chloride channel mutations, participants with sodium mutations had an earlier age of onset of stiffness (5 years versus 10 years), frequent eye closure myotonia (73.5% versus 25%), more impairment on the Individualized Neuromuscular Quality of Life summary score (20.0 versus 9.44), and paradoxical eye closure myotonia (50% versus 0%). Handgrip myotonia was seen in three-quarters of participants, with warm up of myotonia in 75% chloride channel mutations, but also 35.3% of sodium channel mutations. The short exercise test showed 510% decrement in the compound muscle action potential amplitude in 59.3% of chloride channel participants compared with 27.6% of sodium channel participants, which increased post-cooling to 57.6% in sodium channel mutations. In evaluation of patients with clinical and electrical myotonia, despite considerable phenotypic overlap, the presence of eye closure myotonia, paradoxical myotonia, and an increase in short exercise test sensitivity post-cooling suggest sodium channel mutations. Outcomes designed to measure stiffness or the electrophysiological correlates of stiffness may prove useful for future clinical trials, regardless of underlying mutation, and include patient-reported stiffness, bedside manoeuvres to evaluate myotonia, muscle specific quality of life instruments and short exercise testing.