Abnormal postexcitatory and interhemispheric motor cortex inhibition in writer's cramp

Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study excitatory and inhibitory stimulation effects in 25 patients with writer's cramp and 25 healthy volunteers. We investigated excitatory and inhibitory corticospinally mediated motor effects in muscles contralateral to the stimulation side as well as interhemispheric inhibition of tonic motor activity in muscles ipsilateral to stimulation. Motor evoked potentials (MEPs) were recorded from both first dorsal interosseus muscles. Motor thresholds at rest and amplitudes and latencies of MEPs obtained during maximal contraction were always bilaterally normal. The duration of postexcitatory inhibition was significantly shortened (168±55 vs. 198±39 ms in normal subjects, P=0.001) and the duration of interhemispheric inhibition prolonged (30.3±6.6 vs. 26±3.9 ms in normal subjects, P < 0.001). Both observations would be compatible with a decreased inhibition of corticospinal and transcallosal outputs of the motor cortex. The results were not influenced by fatigue effects. Abnormal motor cortex inhibition seems to be a generalized phenomenon in writer's cramp since it was detected in both hemispheres and during a simple isometric motor task which did not evoke dystonic symptoms. Received: 28 February 2000 / Received in revised form: 29 June 2000 / Accepted: 1 August 2000     

Abnormal dorsal premotor–motor inhibition in writer's cramp

The authors hypothesized that a deficient premotor–motor inhibitory network contributes to the unwanted involuntary movements in dystonia. The authors studied nine controls and nine patients with writer's cramp (WC). Dorsal premotor–motor cortical inhibition (dPMI) was tested by applying conditioning transcranial magnetic stimulation (TMS) to the dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6 ms. The authors used an H‐reflex in flexor carpi radialis paired with TMS over the premotor cortex to assess for spinal cord excitability change. Finally, the authors interrupted a choice reaction time task with TMS over dorsal premotor cortex to assess performance in a nondystonic task. The results showed that WC patients exhibited dPMI at rest (88.5%, the ratio of conditioned to unconditioned test pulse), in contrast to controls, who did not show dPMI (109.6%) (P = 0.0198). This difference between patients and controls persisted during contraction (100% vs. 112%) and pen‐holding (95.6% vs. 111%). The H‐reflex in the arm was not modulated by the premotor cortex stimulation. The WC patients made more errors, and the error rate improved with TMS over the premotor cortex. These results suggest that abnormal premotor–motor interactions may play a role in the pathophysiology of focal dystonia. The dPMI was not modulated by task in either group, but was constantly greater in the patients. The significance of the increased inhibition is likely to be compensatory. It appears to be a robust finding and, in combination with other features, could be further explored as a biomarker. © 2014 International Parkinson and Movement Disorder Society     

Abnormal spinal interactions from hand afferents to forearm muscles in writer's cramp.

OBJECTIVE: Spinal reflexes from hand to wrist muscles were investigated in writer's cramp. METHODS: Stimulus-triggered rectified EMG averages after ulnar nerve and cutaneous stimulation, in wrist flexors and extensors during tonic contraction, were compared in 18 controls and 19 patients. RESULTS: On the patient dystonic side, ulnar-induced EMG suppression was decreased in wrist extensors, and facilitation in wrist flexors modified dependent on the dystonic wrist posture during writing. No change was found on the patient non-dystonic side. Cutaneous stimulation increased wrist flexor EMG on both sides of the patients with normal wrist posture during writing, but had no effect in controls and patients with abnormal wrist posture. CONCLUSIONS: Comparison between cutaneous and mixed nerve stimuli suggests that spindle afferents from intrinsic hand muscles may mediate patients' ulnar-induced EMG modulations. Abnormal proprioceptive control was only observed on dystonic side, while bilateral unusual cutaneous control was found in patients. Changes in spinal transmission were partly related to the dystonic wrist posture, suggesting that systems involved in sensory processing can be differentially altered in writer's cramp. SIGNIFICANCE: Changes in spinal transmission, probably related to peripheral and/or cortical inputs, might either take part in primary or adaptive mechanisms underlying writer's cramp.     

EMG-EMG coherence in writer's cramp.

We investigated the extent to which oscillatory drives to muscle, believed to arise mainly from the motor cortex, are exaggerated and/or fail to react normally to peripheral stimulation in writer's cramp. We used the coherence between active forearm flexor and intrinsic hand muscles as our index of such drives before and after digital nerve stimulation of the dominant hand. The results in 8 patients with writer's cramp were compared with those in eight age- and sex-matched healthy subjects. We found no significant difference in either the strength of intermuscular coherence or its modulation by cutaneous stimulation between patients and healthy subjects during voluntary flexion of the wrist and extension-abduction of the fingers. Therefore, we were unable to provide evidence for a pervasive disturbance of oscillatory cortical motor outflow in writer's cramp.     

Abnormal contingent negative variation in HIV patients receiving antiretroviral therapy

The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virally suppressed patients and controls on neuropsychological measures of psychomotor speed, selective attention and mental flexibility. These results suggest that antiretroviral therapy may not be effective in protecting cortical and subcortical structures against HIV-related neuropathology, regardless of immune function. However, the benefits of antiretroviral therapy on immune function appear to facilitate neurocognitive performance.     

Cognitive response control in writer's cramp

Disturbances of the motor and sensory system as well as an alteration of the preparation of movements have been reported to play a role in the pathogenesis of dystonias. However, it is unclear whether higher aspects of cortical - like cognitive - functions are also involved. Recently, the NoGo-anteriorization (NGA) elicited with a visual continuous performance test (CPT) during recording of a 21-channel electroencephalogram has been proposed as an electrophysiological standard-index for cognitive response control. The NGA consists of a more anterior location of the positive area of the brain electrical field associated with the inhibition (NoGo-condition) compared with that of the execution (Go-condition) of a prepared motor response in the CPT. This response control paradigm was applied in 16 patients with writer's cramp (WC) and 14 age matched healthy controls. Topographical analysis of the associated event-related potentials revealed a significant (P < 0.05) NGA effect for both patients and controls. Moreover, patients with WC showed a significantly higher global field power value (P < 0.05) in the Go-condition and a significantly higher difference-amplitude (P < 0.05) in the NoGo-condition. A source location analysis with the low resolution electromagnetic tomography (LORETA) method demonstrated a hypoactivity for the Go-condition in the parietal cortex of the right hemisphere and a hyperactivity in the NoGo-condition in the left parietal cortex in patients with WC compared with healthy controls. These results indicate an altered response control in patients with WC in widespread cortical brain areas and therefore support the hypothesis that the pathogenesis of WC is not restricted to a pure sensory-motor dysfunction.     

Prospective clinical study of writer's cramp.

Sixty-five consecutive patients with writer's cramp were studied prospectively to evaluate clinical and demographic features, the number of writing hours per day at dystonia onset, and the existence of trigger events. Assessment of writing and drawing was done on a standardized test using categorical scales. The importance of subjective handicap and pain, of postural and action tremor, the abnormal features of hand grip and the occurrence of mirror dystonia (dystonia occurring in the dominant hand when writing with the other hand) were studied. Thirty-two patients had simple writer's cramp, whereas the others had complex writer's cramp with several activities other than writing involved. No significant differences were seen in age of onset, legibility, pain, and handicap in these two groups. Seven patients had a family history of focal dystonia and six of them had a complex form of writer's cramp. Mirror dystonia was seen in 29 patients and in some it appeared useful to distinguish dystonic movements from secondary compensatory strategies.     

Psychiatric aspects of writer's cramp

Summary Although its aetiopathogenesis is still unknown, writer's cramp is meanwhile regarded essentially an organically induced disorder. However, as shown by this interdisciplinary study, psychodynamic factors should not be neglected. Special attention should be given to the patients' experience of the syndrome and secondary psychoreactive processes.     

Movement-related cortical potentials in writer's cramp

Movement-related cortical potentials in response to simple, self-paced, brisk index finger abduction movements were recorded in patients with simple and complex writer's cramp and compared with those of age-matched control subjects. Analysis of the movement-related cortical potential waveforms showed that the Bereitschaftspotential, the peak of the negative slope, and the frontal peak of the motor potential did not differ in the two groups, except for the average amplitude of the early part of the negative-slope peak, which was decreased in the patient group during the interval of 300 to 200 msec prior to electromyographic onset. This finding was restricted to the electrodes overlying the contralateral and midline central electrodes. Movement-related cortical potentials from patients and control subjects could be equally accounted for by a four-dipole source model with sources located in the contralateral and ipsilateral sensorimotor regions and the supplementary motor area. There was a trend for a reduction in the strength of the sensorimotor sources active during the premotor period in the patient group, but the difference did not reach a significant level for any individual source. No differences were found between the movement-related cortical potentials elicited by movements of the affected and unaffected hand, or between those of patients with simple or complex hand cramps. This result suggests a deficiency of contralateral motor cortex activation just prior to the initiation of voluntary movements in patients with focal dystonia.     

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.     

How to assess motor impairment in writer's cramp.

Writer's cramp is a task-specific hand dystonia affecting handwriting. Clinical scores such as the Arm Dystonia Disability Scale (ADDS) or Writer's Cramp Rating Scale (WCRS) as well as kinematic analysis of handwriting movements have been used to assess functional impairment in affected patients. In 21 patients with writer's cramp and healthy controls, we analyzed the kinematics of writing and cyclic drawing movements. We rated the severity of dystonia using the ADDS and WCRS and correlated the clinical scores with movement kinematics. Mean stroke frequency was significantly reduced in dystonic patients. Drawing movements showed more frequently a decrease in stroke frequency than handwriting movements. During circle drawing, mean vertical peak velocity was more variable in patients relative to controls, indicating an impaired ability to reproduce the same kinematic pattern over time. An increase in vertical writing pressure was only observed during handwriting but not during circle drawing and may reflect a compensatory effort to stabilize the pencil. Kinematic measures and individual ADDS and WCRS scores did not correlate with each other. The lack of correlation is not surprising as ADDS, WCRS, and kinematic analysis probe different aspects of motor impairment. The ADDS characterizes how dystonia affects a set of fine manual tasks, whereas the WCRS scores the manifestation of dystonia during handwriting. Therefore, the clinical scores and kinematic analysis of handwriting provide complementary insights into motor impairment. Future studies need to address which combination of clinical scores and kinematic measures are most appropriate to quantify impairment in writer's cramp.     

Botulinum toxin therapy of writer's cramp

The pathophysiology and management of writer's cramp is one of the most challenging amongst the various forms of focal dystonias. Frequently, the dystonic postures are confounded by compensatory muscle activity. Correct identification of target muscles for botulinum toxin (BT) injections determines the treatment success. The dosages of different preparations vary, with 1 unit of Botox® roughly equalling 3.5 units of Dysport®. Electromyographic guided injections yield better results and may also decrease the amount of toxin required. Weakness of target muscles interfering with other non‐writing activities is a frequently encountered adverse effect. Studies have shown that BT is a safe long‐term therapy option.     

书写痉挛的立体定向治疗

目的回顾性分析9例书写痉挛患者的立体定向手术治疗的方法及疗效,探讨书写痉挛患者的治疗机制。方法运用脑深部微电极引导下的立体定位技术,对9例药物治疗无效及符合手术指证的书写痉挛患者行丘脑腹外侧核团损毁术,并分析其治疗效果。结果 9例患者即刻恢复书写功能,术后随访,无手术并发症,2³ y的随访中,1例患者复发,余8例患者随访疗效稳定。结论立体定向丘脑腹外侧核团损毁术是书写痉挛的安全有效的治疗手段。     

书写痉挛患者感觉运动整合功能的异常

书写痉挛患者发病机制仍不明确,神经电生理和神经影像学的研究揭示了感觉运动整合的异常在其中起到重要的作用,并为其治疗提供了新的可能.