Clonus is explained from increased reflex gain and enlarged tissue viscoelasticity

Upper motor neuron diseases (UMND), such as stroke and spinal cord injury (SCI), are assumed to produce alterations in muscle tissue in association with neural damage. Distinguishing between these two factors is of clinical importance in choosing appropriate therapy. We studied the effect of changes in the gain of the Ia reflex pathway and tissue viscoelasticity on the emergence, frequency, and persistence of ankle clonus: a clinically significant, involuntary oscillatory movement disorder. Monte Carlo simulations were performed to explain our experimental observations in patients with stroke (n = 3) and SCI (n = 4) using a nonlinear antagonistic muscle model of the human ankle joint. Ia reflex gain was varied by changing motor unit pool threshold and gain, and passive tissue viscosity and elasticity were varied by changing optimal muscle length. Tissue viscoelasticity appeared to have a strong effect on the emergence and persistence of clonus. Observed frequencies of ankle movement, prior to and after the experimental intervention of a sudden damper, was predicted by the model. The simulations revealed that reflex gains were largest in patients with the largest tissue viscoelasticity. We conclude that ankle clonus in stroke and SCI is the result of a combination of, and suggests a relation between, (i) a decrease in threshold and an increase in gain of the motor unit pool and (ii) a decrease in optimal muscle length.     

Studies on the excitability of the central program generator in the spinal cord of the terrapin Pseudemys scripta elegans

We present observations on the multicyclic scratch reflex in spinal terrapins as produced by electrical stimuli applied to the shell at the specific regions at which a mechanical stimulus produces the reflex. EMGs and hip and knee movements are recorded. The responses to the electrical stimuli are similar to the responses to mechanical stimuli. There is a three phase EMG pattern (Stein and Grossman, 1980), to which the movement pattern is related (Bakker and Crowe, 1982). A response may consist of a series of up to 25 movement cycles with a total time course of up to about 30 sec. The initial cycles of a response are relatively fast (less than 1 sec), but the cycles at the expiration of the response may have a duration of 2-3 sec. A single electrical stimulus pulse is often insufficient to trigger a series response. Instead, a weak EMG burst of a few tenths of a second duration, together with a slight movement, is often seen. However, a second pulse can set the cycle series in motion even after an interval of 40 sec between the pulses. A further booster stimulus pulse given while a reflex response is taking place can increase the speed of the movement. If the booster pulse is given just after cessation of reflex activity it can restart the activity, but this second cycle series is often shorter than the first one. The results indicate that the excitability of the central program generator is not constant. Long duration changes in the excitability are produced within the spinal cord.     

The range of control of the afferent system of the flexor reflex]

The control processes caused by the action of electric inhibition of the nerve fibres and depolarized and hyperpolarized influences in the neurones structures of the spinal cord are discussed. Three typical bands of the amplitude control of motor apparatus in the multineuronic reflex ring are distinguished. The transmission of the action potentials in the battle control bands is carried out by the double way modulation. The first band is characterized by the most effective control with amplitude of the signal control in the limit of three thresholds. In the third band the transmission of information is possible in the inversion regime with unsteady polarity of the reflex movement. The second band unfits for the transmission of control commands.     

低氧对横断脊髓大鼠脊髓反射兴奋性的影响

本文用低压舱模拟不同海拔高度,测定横断脊髓大鼠脊髓反射兴奋性恢复曲线。断脊髓组和对照组自海拔２０００ｍ以后脊髓反射兴奋性逐渐增高,但两组出现差异有显著性的海拔高度不同,断脊髓组为海拔４０００ｍ,对照组为海拔３０００ｍ。对照组与断脊髓组在同一海拔高度上比较,除海拔３０００ｍ时差别有显著性（Ｐ＜０．０５）外,在其它各海拔高度上两组间差异无显著性（Ｐ＞０．０５）。结果表明,低氧时脊髓以上中枢和脊髓都参与脊髓反射兴奋性升高的调节     

Decreased cutaneous sensory axon-reflex vasodilatation below the lesion in patients with complete spinal cord injury

The histamine-induced skin flare response has been considered of practical value in determining the level of a spinal cord lesion, but clinical observations have varied widely with regard to the nature and degree of change below the lesion. We have quantified cutaneous sensory axon-reflex vasodilatation in patients with complete spinal cord injury (SCI) above and below the lesion, and compared the findings with normal subjects. Axon-reflex vasodilatation was induced by intradermal histamine injection, and measured by (a) laser Doppler fluxmetry and (b) tracing the surface area of the flare. Axon-reflex vasodilatation was present in all SCI patients above and below the lesion, but was significantly diminished below the lesion by both measures (pflux rise = 0.0008; pflare = 0.023), and in comparison with controls (by 39%). The flux increase was significantly correlated with the area of flare (r = 0.82; p = 0.02). Axon-reflex vasodilatation and visual analogue scale (VAS) pain scores on histamine injection were not significantly different above the lesion in SCI patients from controls. Baseline laser Doppler flux was not different at any test site in SCI and normal subjects. The cutaneous sensory axon-reflex is thus significantly diminished in SCI patients below the level of the lesion, but the underlying mechanism is unclear. A possible explanation under investigation is that increased basal or reflex sympathetic vasoconstriction mediated via the isolated spinal cord may counteract the vasodilatation produced by the cutaneous sensory terminals.     

Remote electrodermic response to an algogenic stimulus. Pathway and spinal integration

The pathway of a non-segmental sudomotor reflex was studied in rabbits (New Zealand white). By means of thermic stimulation (45 degrees during 30") at the lateral border of the foot, a sudoral response was evoked in a circumscribed area of the pinna. By sequential sections of different nerves and the nervous network around the saphenous and femoral vessels, it was possible to establish the following afferent pathways to the spinal cord: lateral plantar nerve, tibial nerve up to the tuber calcanei, saphenous perivascular network, femoral perivascular network and femoral nerve. The fibres responsible for the podo-auricular sudomotor reflex penetrate into the spinal cord above L4, because the spinal transection at this level does not alter the auricular response. Since the hemisection of the spinal cord at T6 suppresses this reflex in the pinna of the same side, it must be concluded that the spinal pathway is ipsilateral. The efferent pathway abandons the spinal cord beneath segment C6: in fact, the spinal transection at C6 does not alter the auricular response to plantar stimulation. Finally, the sudomotor impulses reach the pinna sweat glands with the auricular vessels.     

Motor unit behavior during clonus.

Medial gastrocnemius surface electromyographic activity and intramuscular electromyographic activity were recorded from six individuals with chronic cervical spinal cord injury to document the recruitment order of motor units during clonus. Four subjects induced clonus that lasted up to 30 s while two subjects induced clonus that they actively stopped after 1 min. Mean clonus frequency in different subjects ranged from 4.7 to 7.0 Hz. Most of the 166 motor units recorded during clonus (98%) fired once during each contraction but at slightly different times during each cycle. Other motor units fired during some clonus cycles (1%) or in bursts (1%). When 59 pairs of units were monitored over consecutive clonus cycles (n = 5-89 cycles), only 8 pairs of units altered their recruitment order in some cycles. Recruitment reversals only occurred in units that fired close together in the clonus cycle. These data demonstrate that orderly motor unit recruitment occurs during involuntary contractions of muscles paralyzed chronically by cervical spinal cord injury, providing further support for the importance of spinal mechanisms in the control of human motor unit behavior.     

Scratch reflex evoked by strychnine applied to the spinal cord

Effective facilitation of the scratch reflex was observed in experiments on recently decerebrated and spinal cats in response to application of strychnine solution to the dorsal surface of the spinal cord. The receptive fields of the scratch reflex in this case depended on the segments to which the strychnine was applied. The receptive fields of a scratch reflex evoked by D-tubocurarine coincided with those of the intact adult animals, but the receptive fields for strychnine application were wider and corresponded to those of the scratch reflex in kittens [1, 10]. It is suggested that strychnine application abolishes the inhibition of the afferent inputs of the scratch reflex in the lower cervical segments of the spinal cord which has developed during ontogeny.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 6, pp. 622–625, November–December, 1978.     

Effect of diaphragm small-fiber afferent stimulation on ventilation in dogs

Little is known regarding the role of diaphragm small-fiber afferents (groups III and IV) in the control of breathing. This study was designed to determine whether activation of these afferents with use of capsaicin affects phrenic efferent activity. Capsaicin injections into the phrenic artery were made in 10 alpha-chloralose-anesthetized dogs after each of the following procedures performed in succession: bilateral cervical vagotomy, C7 spinal cord transection, bilateral cervical dorsal rhizotomy. In six of these animals injections were also made after C2 spinal cord transection and removal of the cervical spinal cord. Injections made in the vagotomized animals were associated with apneusis followed by hyperpnea. C7 spinal transection eliminated the hyperpneic response, but the apneusis remained. Cervical dorsal rhizotomy or C2 spinal cord transection failed to abolish the apneusis in response to injection. No diaphragm response was obtained after removal of the cervical spinal cord. Experiments in three additional animals showed that capsaicin does not have a direct excitatory effect on the muscle cells of the crural diaphragm, nor does it potentiate the release of neurotransmitter in the diaphragm. The results of this study indicate that small-fiber afferents in the diaphragm have an excitatory effect on phrenic motoneurons. There is a segmental component to this reflex, since the response is observed after C2 spinal cord transection. The data also suggest that at least some of these afferents enter the spinal cord through the ventral roots.     

Role of reflex gain and reflex delay in spinal stability--a dynamic simulation

The goal of this study was to investigate the role of reflex and reflex time delay in muscle recruitment and spinal stability. A dynamic biomechanical model of the musculoskeletal spine with reflex response was implemented to investigate the relationship between reflex gain, co-contraction, and stability in the spine. The first aim of the study was to investigate how reflex gain affected co-contraction predicted in the model. It was found that reflexes allowed the model to stabilize with less antagonistic co-contraction and hence lower metabolic power than when limited to intrinsic stiffness alone. In fact, without reflexes there was no feasible recruitment pattern that could maintain spinal stability when the torso was loaded with 200N external load. Reflex delay is manifest in the paraspinal muscles and represents the time from a perturbation to the onset of reflex activation. The second aim of the study was to investigate the relationship between reflex delay and the maximum tolerable reflex gain. The maximum acceptable upper bound on reflex gain decreased logarithmically with reflex delay. Thus, increased reflex delay and reduced reflex gain requires greater antagonistic co-contraction to maintain spinal stability. Results of this study may help understanding of how patients with retarded reflex delay utilize reflex for stability, and may explain why some patients preferentially recruit more intrinsic stiffness than healthy subjects.     

Descending modulation of reflex reactions in spinal motoneurons produced by spinal cord injury in man

A study was made of changes in the amplitude of H-reflexes in m. gastrocnemius and the intensity of Ia inhibition in healthy subjects versus patients with midthoracic injury to the spinal cord before, during, and after voluntary tensing of the masticatory, cervical, and finger muscles. Tensing these muscles brought about facilitation of H-reflex and reduced intensity of Ia response in healthy subjects and patients with paraparesis but produced the opposite effect on paraplegics (or had no influence on reactions). This leads to a discussion of the relationship between the changes observed in reflex reactions and posttrauma damage to structure and function of the spinal cord.A. A. Bogomolets Institute, of Physiology, Academy of Sciences of the Ukrainian SSR. Kiev. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 105–113, January–February, 1988.     

Peculiarities of spinal hyperreflexia after combined synchronous transection of the sciatic nerve and chordotomy in rats

Parameters of the reflex discharges evoked by spinal dorsal root stimulation were measured in rats with the sciatic nerve and spinal cord (at low thorasic level) transected five days earlier. Monosynaptic discharges in the ventral roots were found to increase after the operation; the degree of increase was significantly higher as compared with that observed after isolated transections of the spinal cord or the nerve. The combined lesion of the nerve and spinal cord could result in the appearance of high-amplitude reflex discharge components, probably of a polysynaptic nature. We concluded, from the comparison of modifications of reflex discharges, that the mechanisms underlying spinal hyperreflexia after nerve or spinal cord lesions differ considerably from each other.Neirofiziologiya/Neurophysiology, Vol. 26, No. 3, pp. 197–202, May–June, 1994.     

扩散张量成像对颈椎病脊髓早期损伤的研究

目的:探讨磁共振(MR)扩散张量成像(DTI)作为定量分析方法,对脊髓型颈椎病(CSM)脊髓早期损伤诊断的应用价值.方法:选择45例经临床及影像诊断为脊髓型颈椎病患者,颈椎常规MRI检查显示脊髓内无异常信号,使用单次激发自旋回波平面(SE-EPI)序列,进行DTI扫描.测量压迫部位脊髓的ADC值及FA值作为病例组,选择病变上或下方两个节段以上未受压正常脊髓作为正常对照组,测量其ADC值及FA值.分析病例组与对照组间ADC及FA值差别,计算ADC值及FA值诊断脊髓损伤的敏感性.结果:所有脊髓型颈椎病患者经DTI检查均可得到ADC图及FA图,经图像后处理,脊髓显示清晰,图像无变形及伪影.3例脊髓型颈椎病患者ADC值降低,42例脊髓型颈椎病患者ADC值增高,平均ADC值为(1.388± 0.149)x 10-3 mm2/s.44名脊髓型颈椎病患者FA值降低,1名脊髓型颈椎病患者FA值增高,平均FA值为0.476±0.085,受压处脊髓平均ADC值升高,平均FA值下降,与正常值比较差别有统计学意义.ADC值诊断的敏感性为93.33％,FA值诊断的敏感性为97.78％.结论:DTI与常规MR比较,能早期而准确地诊断脊髓型颈椎病脊髓早期损伤.     

Effects of different vibration frequencies on spinal cord reflex circuits and thermoalgesic perception

Objectives:We studied the effect of different vibration frequencies on spinal cord excitability and heat pain perception. We hypothesized that the effects of vibration on spinal cord reflexes, and, also those on heat pain perception, depend on vibration frequency.Methods:In 9 healthy subjects, we applied vibration over the tibialis anterior muscle at three different frequencies (50, 150, or 250 Hz) on spinal cord reflex excitably, tested with the H reflex and the T wave in the soleus muscle, as well as on sensory and pain perception, tested by measuring warm perception (WT) and heat pain perception thresholds, (HPT) in sites rostral and caudal to vibration. Exams were carried out before, during, and after vibration.Results:The amplitude of the H reflex and T wave significantly decreased during vibration in comparison to baseline. Low frequencies (50 and 150Hz) induced greater reflex suppression than high frequency (250Hz). No significant changes were observed on WT and HPT.Conclusions:The effects of vibratory stimulation can be summarized as frequency-related suppression of the spinal cord excitability without an effect on warm and heat pain perception. The present results may help to design vibration-related interventions intended to diminish spinal cord reflex excitability in spastic patients.     

L’erection et l’ejaculation psychogenes: Mythe ou realite? Intérêt de leur recherche chez le blessé médullaire

Erection and ejaculation can be induced by two forms of stimulation. The first is mechanical: touching of the penis, scrotum and anus stimulates the pudendal nerves and a reflex erection appears via the parasympathetic pathway. The second form of sexual stimulation is psychological: erotic pictures and fantasies stimulate the splanchnic nerves and the hypogastric plexus, via the orthosympathetic dorso-lumbar pathway, and induce a psychogenic erection. Spinal injury can destroy a part of these neurological routes and cause impotence and/or failures of ejaculation. We have studied 35 patients reporting a sexual dysfunction after a spinal injury, and have tried to generate an erection and ejaculation first with mechanical stimulation, and then with erotic pictures without mechanical genital stimulation. Tumescence was registered using a plethysmograph and semen was collected in order to study spermatogenesis. The spinal cord was destroyed in 12 patients, but orthosympathetic stimulation produced a psychogenic erection in 15 cases, followed by ejaculation in six cases. This form of stimulation seems to be better than prostaglandin or electrical stimulation.     

脐带间充质干细胞移植治疗脊髓损伤的临床研究

目的:探讨脐带间充质干细胞移植治疗脊髓损伤的疗效及安全性。方法:40例脊髓损伤患者给予脐带间充质干细胞移植治疗,移植方法采用静脉输注联合腰穿鞘内注射的方法。术后随访1年余定期观察患者临床症状及各项指标的变化并进行综合分析。移植过程中为促进干细胞的生长和分化,根据患者病情及身体状况给予相应的康复功能锻炼。结果:与入院时比较,脐带间充质干细胞移植治疗3、6、12个月后,不完全性脊髓损伤患者针刺觉评分、轻触觉评分、运动评分均有明显改善(P<0.05或0.01),完全性脊髓损伤患者针刺觉评分、轻触觉评分、运动评分均无明显变化(P>0.05),两组残损分级均无明显改善(P>0.05)。移植后各项生化指标正常,未出现严重的并发症和明显的不良反应。结论:脐带间充质干细胞移植治疗脊髓损伤近期疗效明显,可以改善患者的临床症状,提高患者的生存质量,是一种值得借鉴的治疗方法。     

Characteristics of the tonic stretch reflex in spastic spinal cord and head-injured patients

Spasticity is a known sequelae of spinal cord injury and head injury. We sought to examine whether there were any significant differences in the characteristics or underlying mechanisms of spasticity in these two groups in the chronic period which may be related to the level of injury of the neuraxis. The response to vibration applied to the muscle, or the tonic vibratory reflex, has been shown to be related to the degree of spasticity, and was therefore studied along with phasic reflexes and passive movements. These studies were carried out on cooperative, stabilized patients who were otherwise healthy, 5 with head injuries, and 5 with spinal cord injuries. The patients were examined in a supine position while surface EMG recordings were made of quadriceps and triceps surae muscles bilaterally. Tendon jerk responses, passive and volitional movements, and responses to a powerful vibratory stimulator were measured. In both head injury and spinal cord injury patient groups, a large EMG response was elicited by passive maneuvers, and tendon jerks were exaggerated. The tonic vibratory response, previously shown to be dependent upon brain influence, was present in both groups. These observations suggest that similar suprasegmental mechanisms may be responsible for hypertonia in both head-injured and spinal cord-injured patients.     

Phantom reflexes: muscle contractions at a frequency not physically present in the input stimuli

In the motor system, the periodic stimulation of one Ia-afferent input produces reflex muscle contractions at the input frequency. However, we observed that when two Ia monosynaptic reflex-afferent inputs are involved the periodic muscle contractions may occur at a frequency physically not present in the afferent inputs even when these inputs are sub-threshold. How can the muscles respond with such phantom reflex contractions at a frequency physically absent in the sub-threshold Ia-afferent input stimuli? Here we provide an explanation for this phenomenon in the cat spinal cord, that we termed “ghost motor response”. We recorded monosynaptic reflexes in the L7 ventral root, intracellular potentials in the motoneurons, and the associated muscular contractions elicited by stimulation of the lateral and medial gastrocnemius nerves. By stimulating with periodic pulses of sub-threshold intensities and distinct frequencies of 2 and 3 Hz the lateral and medial gastrocnemius nerves, respectively, we observed monosynaptic responses and phantom reflex muscle contractions occurring at the fundamental frequency (1 Hz), which was absent in the input stimuli. Thus we observed a reflex ghost motor response at a frequency not physically present in the inputs. We additionally studied the inharmonic case for sub-threshold stimuli and observed muscular contractions occurring at much lower frequencies, which were also conspicuously absent in the inputs. This is the first experimental evidence of a phantom reflex response in the nervous system. The observed behavior was modeled by numerical simulations of a pool of neurons subjected to two different input pulses.     

Study of Hoffmann's reflex of the soleus muscle during spinal shock in man]

The Hoffmann's reflex of the soleus muscle, was studied in 14 patients mith complete spinal cord section and spinal shock. This H reflex was absent in most of the cases seen before the 24th hour. In others or in subjects later examined, there was some abnormalities of the recruitement and recovery curves-wich progressively disappeared. These date bring new understandings on the pathophysiology of the spinal shock wich, even in man, early corresponds to a complete depression of the alpha-motoneurone excitability.