Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp.

Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities.     

Prevalence of primary late-onset focal dystonia in the Belgrade population.

The aim of this cross-sectional study was to estimate the prevalence of different subtypes of idiopathic focal dystonia in the population of Belgrade (Serbia), Yugoslavia. On December 31, 2001, the crude prevalence of all studied types of dystonia (focal, segmental, and multifocal) in Belgrade was 13.6 per 100,000 population (11.8 per 100,000 for men and 15.2 per 100,000 for women). Type-specific prevalence for focal dystonia was 11.2 per 100,000. The prevalence for cervical dystonia, blepharospasm, writer's cramp and laryngeal dystonia were 5.9 per 100,000, 1.9 per 100,000, 1.9 per 100,000, and 1.1 per 100,000, respectively.     

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.     

针药结合治疗书写痉挛症32例疗效观察

采用针灸配合药物治疗书写痉挛症32例,另设单纯药物治疗30例为对照组,观察两组的临床疗效.结果:观察组总有效率为97%,对照组总有效率为83%.经统计学处理,P＜0.05,两组间差异有显著性.提示:观察组疗效优于对照组.     

Modulation of reflex responses in hand muscles during rhythmical finger tasks in a subject with writer’s cramp

The objective of this study was to examine phase- and task-dependent modulation of stretch reflexes during repetitive finger movements in writer’s cramp, and compare them with normal controls from our previous study. A subject with writer’s cramp conducted two rhythmic tasks, index finger abduction (RFA) and a pen-squeezing (RPS) task akin to handwriting. Stretch reflexes were evoked by mechanical perturbations at random phases of each task. Surface electromyograms (EMG) were recorded from two hand muscles, first dorsal interosseous (FDI) and flexor digitorum superficialis (FDS). The reflex response and background EMG activity of each muscle were modulated in a phase-dependent manner in both tasks. However, they varied largely in phase during the RFA task, but in approximately inverse phase-relationship during RPS. Reflex sensitivity, as represented by the slope of the linear regression between response and background, was much lower for both muscles in the ‘writing’ task (RPS) than in the RFA task with its positively correlated responses. These phase- and task-related modulation patterns differed dramatically from those observed in our control subjects, where reflex responses were modulated largely in phase with background activity and reflex sensitivity was much higher, particularly in FDI during RFA and FDS during RPS. The altered reflex modulation patterns in writer’s cramp may reflect deficiencies of integration of proprioceptive afferent inputs and reduced inhibition at cortical and spinal levels during writing performance. Results from this case study support clinically identified task-specific feature of focal hand dystonia.     

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。     

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     

Cerebral activation patterns in patients with writer's cramp: a functional magnetic resonance imaging study

Functional MRI (fMRI), visualizing changes in cerebral blood oxygenation, has to date not been performed either in patients with writer's cramp or in healthy subjects during writing. We compared the cerebral and cerebellar activation pattern of 12 patients with writer's cramp during writing with a group of 10 healthy subjects performing the same tasks over 30-s periods of rest or writing. Sixty echo planar imaging multi-slice datasets were analysed using SPM96 software. Data were analysed for each subject individually and groupwise for patients vs. controls. Healthy subjects showed a significant activation of the ipsilateral dentate nucleus, contralateral cerebellar hemisphere, contralateral primary sensorimotor cortex, and contralateral precentral gyrus during writing. Patients with writer's cramp showed significantly greater activation of the ipsilateral cerebellar hemisphere than controls. Also the activation in the primary sensorimotor cortex extended further caudally and anteriorly towards the premotor association area. Activation was observed in the thalamus during writing only among the patients. Our results indicate an increased basal ganglia output via the thalamus to the motor and premotor cortical areas in dystonia patients and support the notion of disinhibition of the motor cortex leading to coconcentrations and dystonic postures. Received: 10 November 1999 / Received in revised form: 4 April 2000 / Accepted: 26 April 2000     

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。     

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.