Glycine: An important potential component of spinal shock

Amino acid neurotransmitters (AANTs) play a major role in maintenance of muscle tone. Abnormal AANT concentrations are associated with hyper- or hypotonic states. Flaccidity from spinal shock commonly occurs after spinal cord injury (SCI) and may be associated with changes in AANT concentrations. Ischemic SCIs created in the lumbar region of rabbits by intraaortic balloon occlusion produced spastic or flaccid injuries. Microdialysis sampling of AANTs from the injured segmental structures was done 3 days after SCI. Evoked potentials were used to monitor spinal cord stability. No significant changes in AANT levels occurred in the spastic or flaccid group after 4 hour sampling. However, flaccid animals had baseline glycine levels 2–3 times higher (p<0.001) than spastic animals or controls. High concentrations of the inhibitory AANT glycine is associated with flaccidity following SCI, or spinal shock, but not spasticity. Glycinergic compounds directed toward suppression of excess muscle tone deserve further study.     

Assessment of post-stroke elbow flexor spasticity in different forearm positions

Abstract

Purpose/Aim: There have been conflicting results regarding which muscle contribute most to the elbow spastic flexion deformity. This study aimed to investigate whether flexor spasticity of the elbow changed according to the position of the forearm, and to determine the muscle or muscles that contributed most to the elbow spastic flexion deformity by clinical examination.

Methods: This study is a single group, observational and cross-sectional study. Sixty patients were assessed for elbow flexor spasticity in different forearm positions (pronation, neutral and supination) with Modified Tardieu Scale. The primary outcome measure was a domain of the Modified Tardieu Scale, the dynamic component of spasticity (spasticity angle).

Results: In general, there was a significant difference between forearm positions regarding spasticity angle (p?<?.001). In pairwise comparisons, median spasticity angles in pronation (70 degrees) and neutral position (60 degrees) were significantly higher than those in supination (57.5 degrees) (adjusted p?<?.001 and adjusted p?=?.003, respectively). However, median spasticity angle in pronation did not differ significantly from those in neutral position in favour of pronation (adjusted p?=?.274).

Conclusions: The severity of spasticity changes according to the elbow position which suggests that the magnitude of contribution of each elbow flexor muscle to spastic elbow deformity is different. Reduction of spasticity from pronation to supination leads us to consider brachialis as the most spastic muscle. Since biceps was suggested to be the least spastic muscle in this study, and also to avoid spastic pronation deformity of the forearm, it should be rethought before performing chemodenervation into biceps muscle.     

Electromyographic analysis of upper limb muscles during standardized isotonic and isokinetic robotic exercise of spastic elbow in patients with stroke

Although it has been reported that strengthening exercise in stroke patients is beneficial for their motor recovery, there is little evidence about which exercise method is the better option. The purpose of this study was to compare isotonic and isokinetic exercise by surface electromyography (EMG) analysis using standardized methods.Nine stroke patients performed three sets of isotonic elbow extensions at 30% of their maximal voluntary isometric torque followed by three sets of maximal isokinetic elbow extensions with standardization of mean angular velocity and the total amount of work for each matched set in two strengthening modes. All exercises were done by using 1-DoF planner robot to regulate exact resistive torque and speed. Surface electromyographic activity of eight muscles in the hemiplegic shoulder and elbow was recorded. Normalized root mean square (RMS) values and co-contraction index (CCI) were used for the analysis.The isokinetic mode was shown to activate the agonists of elbow extension more efficiently than the isotonic mode (normalized RMS for pooled triceps: 96.0 ± 17.0 (2nd), 87.8 ± 14.4 (3rd) in isokinetic, 80.9 ± 11.0 (2nd), 81.6 ± 12.4 (3rd) in isotonic contraction, F[1, 8] = 11.168; P = 0.010) without increasing the co-contraction of muscle pairs, implicating spasticity or synergy.     

Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI

Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, recovery from SCI typically involves long term rehabilitation. While recovery of walking ability is a primary goal in many patients early after injury, those with a motor incomplete SCI, indicating partial preservation of volitional control, may have the sufficient residual descending pathways necessary to attain this goal. However, despite physical interventions, motor impairments including weakness, and the manifestation of abnormal involuntary reflex activity, called spasticity or spasms, are thought to contribute to reduced walking recovery. Doctrinaire thought suggests that remediation of this abnormal motor reflexes associated with SCI will produce functional benefits to the patient. For example, physicians and therapists will provide specific pharmacological or physical interventions directed towards reducing spasticity or spasms, although there continues to be little empirical data suggesting that these strategies improve walking ability.In the past few decades, accumulating data has suggested that specific neuromodulatory agents, including agents which mimic or facilitate the actions of the monoamines, including serotonin (5HT) and norepinephrine (NE), can initiate or augment walking behaviors in animal models of SCI. Interestingly, many of these agents, particularly 5HTergic agonists, can markedly increase spinal excitability, which in turn also increases reflex activity in these animals. Counterintuitive to traditional theories of recovery following human SCI, the empirical evidence from basic science experiments suggest that this reflex hyper excitability and generation of locomotor behaviors are driven in parallel by neuromodulatory inputs (5HT) and may be necessary for functional recovery following SCI. The application of this novel concept derived from basic scientific studies to promote recovery following human SCI would appear to be seamless, although the direct translation of the findings can be extremely challenging. Specifically, in the animal models, an implanted catheter facilitates delivery of very specific 5HT agonist compounds directly onto the spinal circuitry. The translation of this technique to humans is hindered by the lack of specific surgical techniques or available pharmacological agents directed towards 5HT receptor subtypes that are safe and effective for human clinical trials. However, oral administration of commonly available 5HTergic agents, such as selective serotonin reuptake inhibitors (SSRIs), may be a viable option to increase central 5HT concentrations in order to facilitate walking recovery in humans. Systematic quantification of how these SSRIs modulate human motor behaviors following SCI, with a specific focus on strength, reflexes, and the recovery of walking ability, are missing.This video demonstration is a progressive attempt to systematically and quantitatively assess the modulation of reflex activity, volitional strength and ambulation following the acute oral administration of an SSRI in human SCI. Agents are applied on single days to assess the immediate effects on motor function in this patient population, with long-term studies involving repeated drug administration combined with intensive physical interventions.     

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.     

A型肉毒毒素治疗上肢痉挛的应用进展

脑瘫、脑卒中、颅脑外伤、多发性硬化等疾病引起上运动神经元病损均可出现肌肉痉挛,给患者的肢体功能造成不良影响。肉毒毒素是肉毒梭状芽孢杆菌产生的一种毒力极强的嗜神经生物毒素,可阻断神经肌肉接头处的乙酰胆碱的释放,导致肌肉松弛性麻痹。一些临床专家利用肉毒毒素(主要为A型肉毒毒素Botulinum toxin type A,BTX-A)的这种生物活性,来治疗肢体肌肉痉挛,已成为相关医学生物学和临床研究的热点之一。     

脑卒中痉挛性患者经颅磁刺激联合物理治疗后上肢功能恢复状况的临床观察

摘要 目的：探讨脑卒中痉挛性患者经颅磁刺激联合物理治疗后上肢功能改善状况的临床观察。方法：选取我院2018年1月到2020年1月共收治的80例脑卒中患者,所有患者均出现不同部位痉挛现象,将患者随机分为观察组与对照组,每组40例。给予对照组患者常规治疗与康复训练,观察组患者在常规治疗基础上应用低频重复经颅刺激联合肌电生物反馈模式下的康复训练。对比两组患者的治疗效果与上肢功能改善情况。结果：观察组治疗总有效率95.00 %,高于对照组72.50 %（P＜0.05）;治疗前两组患者的NIHSS评分应用神经功能缺损量表（Neurological deficit scale,NIHSS）、MMSE评分应用认知功能量表（Cognitive function scale,MMSE）、ADL评分应用日常生活能力量表（Activities of daily living scale,ADL）评分对比无显著差异（P＞0.05）,治疗后,观察组的NIHSS评分低于对照组,ADL评分高于对照组（P＜0.05）;治疗前两组患者的肱二头肌和肱三头肌均方根值（Root mean square,RMS）对比无显著差异（P＞0.05）,治疗后,观察组患者的肱二头肌RMS低于对照组,肱三头肌RMS高于对照组（P＜0.05）;治疗前两组患者的运动功能评估表中的上肢功能部分（Upper limb function in motor function assessment table,FMA-UE）、手部精细化动作及上肢功能测量表（Measurement table of hand fine movement and upper limb function,Carroll）评分对比无显著差异（P＞0.05）,治疗后,观察组患者的FMA-UE、Carroll评分高于对照组（P＜0.05）。结论：对脑卒中上肢痉挛患者在常规治疗与康复训练的基础上应用低频重复经颅刺激联合肌电生物反馈模式下的康复训练,虽然对患者的认知功能无明显影响,但是能提升患者上肢痉挛的治疗效果,促进患者上肢功能恢复,提高生活能力,值得临床应用推广。     

Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia

Mmutations in paraplegin, a putative mitochondrial metallopeptidase of the AAA family, cause an autosomal recessive form of hereditary spastic paraplegia (HSP). Here, we analyze the function of paraplegin at the cellular level and characterize the phenotypic defects of HSP patients' cells lacking this protein. We demonstrate that paraplegin coassembles with a homologous protein, AFG3L2, in the mitochondrial inner membrane. These two proteins form a high molecular mass complex, which we show to be aberrant in HSP fibroblasts. The loss of this complex causes a reduced complex I activity in mitochondria and an increased sensitivity to oxidant stress, which can both be rescued by exogenous expression of wild-type paraplegin. Furthermore, complementation studies in yeast demonstrate functional conservation of the human paraplegin-AFG3L2 complex with the yeast m-AAA protease and assign proteolytic activity to this structure. These results shed new light on the molecular pathogenesis of HSP and functionally link AFG3L2 to this neurodegenerative disease.     

The influence of glycine and related compounds on spinal cord injury-induced spasticity

Spasticity is a frequent and complex sequel to spinal cord injury. The neurochemical basis for the origin of spasticity is largely unknown. Glycine is among the most abundant neurotransmitters in the spinal cord. However, the role of glycine and related compounds in spasticity have received little attention. An ischemic spinal cord injury was created in rabbits, by an intraaortic balloon occlusion technique, which produced lower limb spasticity. A catheter was inserted into the cisterna magna and the spinal cord was bathed with 100 M solutions of glycine, strychnine,d-serine, -alanine, MK-801, or artificial CSF for 4 hours at a rate of 10 l/min. H-reflexes were monitored before and during infusion by stimulating the posterior tibial nerve and recording from the plantar surface of the foot. Glycine,d-serine, and MK-801 depressed the H wave, strychnine produced a heightened H wave, and -alanine caused no significant changes. These results indicate that glycine and related compounds may influence spasticity.