Trends in the pathophysiology and pharmacotherapy of spasticity

Summary Spasticity develops after supraspinal or spinal lesions of descending motor systems, with obligate involvement of the corticospinal tract. Spasticity is characterized by an increase in muscle tone, which, in contrast to many other types of enhanced muscle tone, shows a marked velocity-dependent increase when the muscle is passively stretched. The pathophysiological mechanisms underlying this spastic muscle tone remain obscure. Three major causes are currently considered possible: (1) changes in the excitability of spinal interneurones; (2) receptor hypersensitivity; (3) formation of new synapses by sprouting. The latter mechanism could account for the long time course over which spastic muscle tone develops in hemiplegic or paraplegic patients, but there is no experimental evidence for this hypothesis. The electromyographic (EMG) gait analysis of patients with spasticity has thrown doubt on the common belief that the velocity-dependent increase in spastic muscle tone is evoked by stretch reflex activity and has led to the idea that spastic muscle tone resides in the muscle fibres themselves. While such a mechanism may contribute to the slowness of active movements in spastic patients, recent experiments on patients with spastic arm paresis have confirmed the classical view that the spastic muscle tone is related to the EMG activity evoked in the passively stretched muscle. This pathological EMG activity is seen during the entire range of the dynamic phase of the stretch, during which a normal muscle exhibits only an early, phasic burst at the highest stretch velocities employed. For the pharmacological treatment of spasticity, substances with different central or peripheral actions are available. Their assumed receptor actions are described, together with their main indications and side-effects. A new way to treat severe spasticity is the continuous intrathecal application of baclofen via an implantable pump. This application has the benefit that the sedative effect of baclofen when applied in high oral dosage is avoided.     

Differential diagnosis of proprioceptive and vestibular deficits using dynamic support-surface posturography

The objective of this study was to evaluate how effective dynamic support-surface posturography could be as a diagnostic tool in patients with balance disorders (proprioceptive or vestibular deficits). Specifically, we studied whether measures of trunk control and simple toe-up rotational perturbations, selected using statistical techniques, could provide a better diagnostic yield than either the analysis of lower-body movements or use of a ‘nulled’ ankle input paradigm. The test subjects were 15 control subjects, five patients with bilateral peripheral vestibular loss (VL) and five patients with selective bilateral, lower-leg proprioceptive loss (PL). Amplitudes and onset latencies of bursts of EMG activity in upper and lower-leg muscles, paraspinals and trapezius muscles, concurrent changes in ankle torque, and peak amplitudes of upper-leg, lower-leg, and trunk angular-velocities were measured. Stimuli included three different types of sudden movements of the support surface, a ‘nulled’ ankle input paradigm, a simple toe-up rotation paradigm, and a combined toe-up rotation and backwards translation of the support surface. All stimuli were tested under eyes-open and eyes-closed conditions. For each type of movement and condition the diagnostic classification accuracy (i.e. the overall sensitivity and specificity) was calculated based on those posturography measures providing the highest diagnostic separation between the three populations. Both patient groups showed increased trunk sway, changed support-surface reaction forces and muscle amplitudes compared with controls for toe-up and ‘nulled’ test conditions. Measures providing the greatest diagnostic utility were the amplitude of trunk-angular velocity (increased in VL subjects, less so in PL), the amplitude of balance-correcting paraspinal responses (increased in VL subjects, decreased in PL subjects), the amplitude of trapezius stabilising responses (increased in both patient groups) for simple toe-up rotations under eyes-closed conditions. We conclude, that diagnosis of balance disorders using dynamic posturography is best achieved using measures of trunk control following pure toe-up rotational perturbations tested under eyes-closed conditions.     

Intrinsic and reflex stiffness in normal and spastic, spinal cord injured subjects

Mechanical changes underlying spastic hypertonia were explored using a parallel cascade system identification technique to evaluate the relative contributions of intrinsic and reflex mechanisms to dynamic ankle stiffness in healthy subjects (controls) and spastic, spinal cord injured (SCI) patients. We examined the modulation of the gain and dynamics of these components with ankle angle for both passive and active conditions. Four main findings emerged. First, intrinsic and reflex stiffness dynamics were qualitatively similar in SCI patients and controls. Intrinsic stiffness dynamics were well modeled by a linear second-order model relating intrinsic torque to joint position, while reflex stiffness dynamics were accurately described by a linear, third-order system relating half-wave rectified velocity to reflex torque. Differences between the two groups were evident in the values of four parameters, the elastic and viscous parameters for intrinsic stiffness and the gain and first-order cut-off frequency for reflex stiffness. Second, reflex stiffness was substantially increased in SCI patients, where it generated as much as 40% of the total torque variance, compared with controls, where reflex contributions never exceeded 7%. Third, differences between SCI patients and controls depended strongly on joint position, becoming larger as the ankle was dorsiflexed. At full plantarflexion, there was no difference between SCI and control subjects; in the mid-range, reflex stiffness was abnormally high in SCI patients; at full dorsiflexion, both reflex and intrinsic stiffness were larger than normal. Fourth, differences between SCI and control subjects were smaller during the active than the passive condition, because intrinsic stiffness increased more in controls than SCI subjects; nevertheless, reflex gain remained abnormally high in SCI patients. These results elucidate the nature and origins of the mechanical abnormalities associated with hypertonia and provide a better understanding of its functional and clinical implications.     

强化胰岛素正确注射方法教育对减少皮肤并发症的影响分析

目的 探讨强化胰岛素正确注射方法教育联合图表标示减少皮肤并发症发生的临床价值.方法 将239例糖尿病患者按出院顺序分为对照组和观察组,出院后均采用腹部顺时针方向按8个注射点轮换注射胰岛素,要求8d内注射点不重复、注射点距离上次注射点≥2 cm;并要求一针一换和按正确方法消毒等;对观察组患者强化正确注射方法的重要性教育,并将注射部位和注射时间以图表标示.出院后6个月时比较2组患者胰岛素正确注射方法执行的差异、注射部位皮肤并发症发生率差异,并分析未正确执行胰岛素注射方法患者皮肤并发症发生率.结果 2组注射方法除正确排气差异无统计学意义,注射前洗手、部位轮换注射8d为一周期、8d内注射点不重复、注射点距离上次注射点≥2 cm、采用正确的消毒方法、针头做到一次性使用观察组均明显好于对照组;注射部位皮肤并发症发生率观察组明显低于对照组;皮肤并发症发生率以注射部位未按周期轮换、8d内注射点有重复及注射点距离上次注射点＜2 cm最高,其次是针头多次使用和未按正确方法消毒.结论 强化胰岛素正确注射方法教育可以提高患者注射胰岛素的可操作性,降低注射部位皮肤并发症发生率.     

How not to bite the bullet: A novel technique for intra operative handling of bullets

Ballistic trauma caused by bullets can be fatal or cause serious injury. Despite the abundance in literature in management of bullet injuries, there is paucity in describing how the operating surgeon should handle the bullet intra operatively. Bullets are important pieces of evidence and evidence preservation becomes the responsibility of the surgeon. We suggest a novel technique in handling bullets intraoperatively which, to the best of our knowledge, has not been published before. We also suggest general recommendations in handling bullets intraoperatively.     

Muscle residual force enhancement: a brief review

Muscle residual force enhancement has been observed in different muscle preparations for more than half a century. Nonetheless, its mechanism remains unclear; to date, there are three generally accepted hypotheses: 1) sarcomere length non-uniformity, 2) engagement of passive elements, and 3) an increased number of cross-bridges. The first hypothesis uses sarcomere non-homogeneity and instability to explain how “weak” sarcomeres would convey the higher tension generated by an enhanced overlap from “stronger” sarcomeres, allowing the whole system to produce higher forces than predicted by the force-length relationship; non-uniformity provides theoretical support for a large amount of the experimental data. The second hypothesis suggests that passive elements within the sarcomeres (i.e., titin) could gain strain upon calcium activation followed by stretch. Finally, the third hypothesis suggests that muscle stretch after activation would alter cross-bridge kinetics to increase the number of attached cross-bridges. Presently, we cannot completely rule out any of the three hypotheses. Different experimental results suggest that the mechanisms on which these three hypotheses are based could all coexist.     

Identifying human bite marks in children

Human bite marks in children are relatively common but are either not recognized as such or, when suspected, not subjected to rigorous forensic assessment. When a human bite mark on a child is identified, the explanation generally given is that it was either self-inflicted or the result of being bitten by another child. Adjudication on whether it is a child or adult bite mark must not be attempted, as there is insufficient evidence to determine this by inspection. However, the bite may show sufficient, unique dental characteristics to identify a perpetrator. Thus, it is vital that a forensic odontologist is involved from the outset. This paper describes the characteristics of human bite marks and emphasises the key role of forensic odontology in possible perpetrator identification.     

不同大小仿膀胱生理牵张力对膀胱平滑肌细胞生物学特性的影响

目的 探索不同牵张力对膀胱平滑肌细胞形态和增殖活性的影响. 方法 膀胱平滑肌细胞复合硅胶材料后对材料施加5％、10％、15％、20％及25％等不同大小的牵张力,共聚焦显微镜下观察细胞形态变化.CCK-8酶标法检测细胞增殖能力,流式细胞仪分析细胞周期并计算细胞增殖指数. 结果 在牵张力作用下膀胱平滑肌细胞呈现“收缩型”形态学改变,由无序的星形舒展状态向相对规则的纺锤状细胞形态迁移变化.CCK-8所测对照组吸光值度A为0.471 ±0.027,各牵张组分别增至1.320±0.094(5％组,P＜0.0001)、1.001±0.029(10％组,P＜0.0001)、0.821 ±0.032(15％组,P＜0.0001)、0.621 ±0.032(20％组,P=0.0004)及0.591±0.056(25％组,P=0.0268).与对照组(29.35±0.55)％相比,细胞增殖指数增加到(55.55±1.05)％(5％组,P＜0.0001),(47.70±0.20)％(10％组,P＜0.0001),(35.40 ±2.10)％(15％组,P＜0.0001),与20％组的(34.85±0.55)％(P =0.1372)和25％组的(30.35 ±0.45)％(P =0.5234)比较差异均无统计学意义. 结论 适当强度牵张力可以调节膀胱平滑肌细胞形态并促进细胞增殖活性,5％形变率的牵张力下细胞增殖最活跃.     

Cyclic stretch influenced expression of membrane connexin 43 in human periodontal ligament cell

Objective

Periodontal ligament (PDL) cells play an important role in preserving periodontal homeostasis and periodontal remodelling in response to mechanical stimulations. Gap junction intercellular communication (GJIC) is essential for homeostasis and many other biological processes of multicellular organisms. While the role of GJIC in mechanotransduction of PDL cells remains largely unknown. In the present study, we examined the influence of cyclic stretch on the expression of membrane gap junction protein connexin 43 (Cx43) in cultured human PDL cells.

Design

Cultured human PDL cells were exposed to 1%, 10% and 20% stretch strains for 0.5 h, 1 h and 24 h. Then the membrane Cx43 protein expression was measured by flow cytometry and the Cx43 mRNA level was measured by real-time polymerase chain reaction.

Results

Half hour and 1 h cyclic stretches with strains up to 20% did not change the expression of membrane Cx43 protein, while 24 h cyclic stretches with 10% and 20% strains down-regulated the expression of membrane Cx43 protein in a strain magnitude-dependent manner. Furthermore, cyclic stretch also changed the Cx43 mRNA level and induced realignment in cells.

Conclusion

The present research provide the first evidence that cyclic stretch influenced the membrane Cx43 protein expression in cultured human PDL cells.