A novel TRPA1 variant is associated with carbamazepine‐responsive cramp‐fasciculation syndrome

Cramp‐fasciculation syndrome (CFS) is a rare muscle hyperexcitability syndrome that presents with muscle cramps, fasciculations, and stiffness, as well as pain, fatigue, anxiety, hyperreflexia, and paresthesias. Although familial cases have been reported, a genetic etiology has not yet been identified. We performed whole‐exome sequencing followed by validation and cosegregation analyses on a father‐son pair with CFS. Both subjects manifested other hypersensitivity‐hyperexcitability symptoms, including asthma, gastroesophageal reflux, migraine, restless legs syndrome, tremor, cold hyperalgesia, and cardiac conduction defects. Most symptoms improved with carbamazepine, consistent with an underlying cation channelopathy. We identified a variant in the transient receptor potential ankyrin A1 channel (TRPA1) gene that selectively cosegregated with CFS and the other hypersensitivity‐hyperexcitability symptoms. This variant (c.2755C>T) resulted in a premature stop codon at amino acid 919 (p.Arg919*) in the outer pore of the channel. TRPA1 is a widely distributed, promiscuous plasmalemmal cation channel that is strongly implicated in the pathophysiology of the specific hypersensitivity‐hyperexcitability symptoms observed in these subjects. Thus, we have identified a novel TRPA1 variant that is associated with CFS as part of a generalized hypersensitivity‐hyperexcitability disorder. These findings clarify the diverse functional roles of TRPA1, and underscore the importance of this channel as a potential therapeutic target.     

书写痉挛的研究进展

书写痉挛是一种原发性、任务特异性、局灶性肌张力障碍,其发病机制主要包括基底节及其连接环路的结构功能障碍、感觉运动系统各层面抑制作用的减弱、大脑皮质可塑性及稳态性异常、感觉运动处理功能障碍等4个方面。治疗上,肉毒素注射安全、有效,但作用时间短,需重复注射。内科药物方便,但效果欠佳。外科手术效果好、疗效稳定,但有手术风险。     

Hand pain other than carpal tunnel syndrome (CTS): the role of occupational factors

Some occupational factors have been implicated in the development of disorders manifested as hand pain. The associations seem to be well documented in processes such as hand-arm vibration syndrome (HAVS) or writer's cramp. There are contradictory data in the literature about the relationships of trigger finger, De Quervain's tenosynovitis (DQT) and tenosynovitis of the wrist with occupational factors. In this article, we review current knowledge about clinical manifestations, case definition, implicated occupational factors, diagnosis and treatment of the most relevant hand pain disorders that have been associated with occupational factors, excluding carpal tunnel syndrome (CTS).     

Cramp‐fasciculation syndrome in patients with and without neural autoantibodies

Introduction: We investigated the clinical, electrophysiological and neural autoantibody characteristics in cramp‐fasciculation syndrome (CFS) patients. Methods: We reviewed Mayo Clinic records from 2000 to 2011 to identify clinically defined CFS patients who underwent neural autoantibody testing. Stored sera of patients who tested positive for antibodies to voltage‐gated potassium channel complex (VGKC complex) were analyzed further for leucine‐rich glioma‐inactivated 1 (LGI1) or contactin‐associated protein‐2 immunoglobulin G (CASPR2‐IgG) antibodies. Results: Thirty‐seven patients were identified. Twelve were seropositive for neural autoantibodies. Clinical manifestations were similar in seropositive and seronegative patients, although central and autonomic neuronal hyperexcitability symptoms were more common in seropositive cases. No patients had a malignancy. Repetitive tibial nerve stimulation at 10 Hz revealed longer afterdischarges in seropositive patients. Two of 7 patients with VGKC‐complex autoimmunity demonstrated LGI1 or CASPR2‐IgG antibodies. Only 2 of 12 seropositive patients required immunotherapy. Conclusions: VGKC‐complex autoimmunity occurs in a minority of CFS patients. Antibody positivity was associated with extramuscular manifestations, typically without malignancy. Target antigens within the VGKC complex remain unknown in most patients. Muscle Nerve 49 :351–356, 2014     

镍钛形状记忆合金锔钉在颅骨凹陷骨折复位固定中的应用

目的 探讨闭合性颅骨凹陷骨折的手术治疗方法。。方法 对16例闭合性颅骨凹陷骨折患者应用镍钛形状记忆合金锔钉将复位之凹陷骨折片与正常颅骨固定。结果 随访5－54个月（平均26个月），无骨片移位与下陷、头皮下无积液、无排异反应或炎症，未见腐蚀，X线示复位固定之骨片与周围颅骨密度肉眼观察无明显异常。病人无精神负担，无不安全感。不影响CT、MR检查。结论 应用镍钛形状记忆合金锔钉固定复位之凹陷骨折骨片可获得良好的固定效果，有机械的回复力，手术操作简单，固定牢固，增强了骨折部位对外力的承受能力，整形效果好，合并症少，是目前较为理想的颅骨凹陷骨折治疗手段。     

The effect of reflexology applied on haemodialysis patients with fatigue,pain and cramps

The research was conducted to evaluate the effect of foot reflexology on fatigue, pain and cramps in haemodialysis patients. The sample consisted of 80 patients in total, 40 intervention and 40 control patients, receiving treatment in the haemodialysis units of two institutions. Data were collected by using a questionnaire, Piper Fatigue Scale and visual analogue scale for measuring the severity of cramp and pain. The intervention group received reflexology treatment for 1 week in three sessions following haemodialysis, each session lasting approximately 30 min. Parametric and non‐parametric tests were used in data analysis. It was determined that reflexology reduced the fatigue subscale scores and total scale scores as well as pain and cramp mean scores in the intervention group. The research results revealed that the severity of fatigue, pain and cramp decreased in patients receiving reflexology.     

简单型书写痉挛患者异常皮质活动的功能磁共振成像研究

目的:利用功能磁共振成像,研究简单型书写痉挛患者的皮质异常功能活动,探讨其病因基础。材料和方法:分别对10名简单型书写痉挛患者和10名健康右利手志愿者进行手指写、执笔写任务期间的功能磁共振成像。使用AFNI软件,对数据经过预处理及反卷积分析等处理,获得患者组和正常组两个任务的平均脑激活图并进行比较。结果:与正常组之间相比较,患者组初级感觉运动区和辅助运动区表现为与执笔写任务相关的更明显的激活,而双侧的后顶叶皮质激活在两个不同任务期间均较正常减弱。结论:简单型书写痉挛患者存在运动和感觉皮质的异常活动,反映了其运动皮质的去抑制和感觉处理过程的障碍,并且感觉处理过程的异常可能在其病因过程中起重要作用。     

Three brothers with a very-late-onset writer's cramp.

Writer's cramp (WC) is a form of focal task-specific dystonia, which is brought on by writing. Although most cases are sporadic, a positive family history is present in 5% to 20% of cases. To date, WC has been reported in several families with primary torsion dystonia, including DYT7, a pure focal dystonia, and in the mixed dystonias, DYT1, DYT6, and DYT13. We describe a family of Bulgarian descent with three brothers presenting with a very-late-onset dystonic WC, compatible with linkage to chromosome 18p.     

Corticospinal excitability during motor imagery of a simple tonic finger movement in patients with writer's cramp.

Motor imagery (MI) is the mental rehearsal of a motor act without overt movement. Using transcranial magnetic stimulation (TMS), we tested the effect of MI on corticospinal excitability in patients with writer's cramp. In 10 patients with writer's cramp and 10 healthy controls, we applied focal TMS over each primary motor area and recorded motor evoked potentials (MEPs) from contralateral hand and arm muscles while participants imagined a tonic abduction of the index finger contralateral to the stimulated hemisphere. In healthy controls and patients, the MEP amplitude in the relaxed first dorsal interosseus muscle (FDI) showed a muscle-specific increase during MI; however, the increase was less pronounced in patients than in healthy controls. In addition, in patients but not in controls, the MEP amplitude also increased in hand and forearm muscles not involved in the imagined movement. This abnormal spread of facilitation was observed in the affected and unaffected upper limb. MI of simple hand movements is less efficient and less focussed in patients with writer's cramp than it is in normal subjects.     

Cooling improves the writing performance of patients with writer's cramp.

Cooling of hand and forearm muscles by immersion in 15 degrees C cold water for 5 minutes improved the writing performance of patients with writer's cramp. Since abnormal processing of muscle spindle afferent discharges contributes to the pathology of writer's cramp, this effect might result from a reduction in muscle spindle activity by lowering muscle temperature. Cooling is a simple, cheap, and safe procedure, providing temporary relief for patients with writer's cramp.