Excessive reflexes in spinal cord injury triggered by electrical stimulation

Interaction of electrocutaneous stimulation with an impaired human motor control system may result in unstable reflex loops causing excessive spastic reactions. These contractions are usually excluded from analysis since the presence of spasm is one of the criteria commonly applied for discarding a contraction. They may, however, provide interesting information on the nature of spasticity. The dorsiflexor muscles of four SCI subjects were activated by means of surface electrical stimulation and the isometric ankle moment was measured. Short bursts of constant stimulation frequency at seven different frequencies (8, 12, 16, 20, 25, 33, 50 Hz) triggered spastic reactions in all subjects. The onset times of spastic activity during an electrically elicited contraction shortened with increased stimulation frequency. A stimulation burst may also have a spasticity reduction effect on a subsequent burst, indicating potential short term therapeutic effects of stimulation on spasticity in isometric conditions.     

SPASTICITY—Its Nature and Treatment

There are a number of physiological means of relaxing spasticity, including active resistive exercise, cold hydrotherapy, heat, electrical stimulation of antagonistic muscles, passive stretch in diagonal movement patterns, and the Von Bechterew reflex. Although none of them will cure spasticity, temporary relaxation may permit a patient to achieve better functioning of an affected joint. The choice of procedure will depend on the nature of the lesion and the muscular distribution of the spasticity.     

Spasticity; its nature and treatment

There are a number of physiological means of relaxing spasticity, including active resistive exercise, cold hydrotherapy, heat, electrical stimulation of antagonistic muscles, passive stretch in diagonal movement patterns, and the Von Bechterew reflex. Although none of them will cure spasticity, temporary relaxation may permit a patient to achieve better functioning of an affected joint. The choice of procedure will depend on the nature of the lesion and the muscular distribution of the spasticity.     

经颅直流电刺激对帕金森病伴快速眼动相睡眠行为障碍患者认知功能及神经功能的影响

摘要 目的：探讨经颅直流电刺激对帕金森病伴快速眼动相睡眠行为障碍患者认知功能及神经功能的影响。方法：选择2018年9月-2019年9月在我院接受治疗的69例帕金森病伴快速眼动相睡眠行为障碍患者,采用随机数表法分为电刺激组（n=35）和对照组（n=34）。对照组给予常规抗帕金森病治疗,观察组在对照组的基础上给予经颅直流电刺激治疗。比较两组临床疗效、蒙特利尔认知评估量表（MoCA）、自主神经症状量表（SCOPA-AUT）、睡眠情况、汉密尔顿抑郁量表(HAMD)、Epworth嗜睡量表（ESS）评分、匹兹堡睡眠指数（PSQI）、帕金森氏病综合评分量表（UPDRS）变化情况。结果：治疗后,电刺激组有效率91.43%（32/35）较对照组70.59%（24/34）显著升高,差异显著（P<0.05）;治疗前,电刺激组与对照组之间认知功能及神经功能结果无差异;治疗后,电刺激组与对照组MoCA均随着时间的推移均呈上升趋势,且电刺激组上升程度较较组更低,SCOPA-AUT均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间临床睡眠情况结果无差异;治疗后,电刺激组与对照组总睡眠时间、睡眠效率均随着时间的推移均呈上升趋势,且电刺激组上升程度较对照组更低,醒觉指数均随着时间的推移呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间抑郁、嗜睡情况无差异;治疗后,电刺激组与对照组抑郁、嗜睡均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间PSQI、UPDRS评分无差异;治疗后,电刺激组与对照组PSQI、UPDRS评分均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）。结论：在帕金森病伴快速眼动相睡眠行为障碍患者中应用经颅直流电刺激效果显著,可有效改善认知功能及神经功能水平。     

Use of functional electrical stimulation in the rehabilitation of patients with incomplete spinal cord injuries

When patients enter the Rehabilitation Centre a therapeutic electrical stimulation programme is immediately initiated. Three groups of patients were identified: (i) those in whom an improvement of both voluntary and stimulated muscle force was observed, (ii) those with an increase in stimulation response only, and (iii) patients in whom no effect of electrical stimulation training could be recorded. Isometric measurement of voluntary and stimulated knee joint torque revealed that in a great number of patients one leg was severely paralysed while the other leg was under sufficient voluntary control. Unilateral two-channel stimulation of knee extensors and the peroneal nerve was proposed as an orthotic aid for this group of patients. Exaggerated extensor tone was observed by assessment of spasticity around the knee joint. A two-channel peroneal stimulator was found to be a useful approach in order to inhibit this tone and thereby help the patients to initiate a step.     

Time-dependent effects of neuromuscular electrical stimulation on changes in spinal excitability are dependent on stimulation frequency: A preliminary study in healthy adults

Neuromuscular electrical stimulation (NMES) can be used as treatment for spasticity. The present study examined differences in time-dependent effects of NMES depending on stimulation frequency. Forty healthy subjects were separated into four groups (no-stim, NMES of 50, 100, and 200?Hz). The un-conditioned H-reflex amplitude and the H-reflex conditioning-test paradigm were used to measure the effectiveness on monosynaptic Ia excitation of motoneurons in the soleus (SOL) muscle, disynaptic reciprocal Ia inhibition from tibialis anterior (TA) to SOL, and presynaptic inhibition of SOL Ia afferents. Each trial consisted of a 30-min period of NMES applied to the deep peroneal nerve followed by a 30-min period with no stimulation to measure prolonged effects. Measurements were performed periodically. Stimulation applied at all frequencies produced a significant reduction in monosynaptic Ia excitation of motoneurons in the SOL muscle, however, only stimulation with 50?Hz showed prolonged reduction after NMES. NMES frequency did not affect the amount of disynaptic reciprocal Ia inhibition and presynaptic inhibition of Ia afferents. The results show a frequency-dependent effect of NMES on the monosynaptic Ia excitation of motoneurons. This result has implications for selecting the optimal NMES frequency for treatment in patients with spasticity.     

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.     

Neuromuscular electrical stimulation for skeletal muscle function

Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle.     

Pulsed subcutaneous electrical stimulation in spinal cord injury: preliminary results

The treatment of long-term, stable para- and quadriplegics with pulsed electrical stimulation for pain control resulted in, anecdotally, a significant number of these individuals showing increased motor function as well as sensory awareness. This small pilot study was conducted in order to assess the hypothesis that pulsed electrical fields can effect diseased neurological function. Thirteen para- and quadriplegic subjects with 18 months of stable neurological signs and symptoms were exposed daily to pulsed electrical stimulation for a 6-month period and assessed for any improvement in motor function or sensory perception. The hypothesis is that pulsed electromagnetic fields can normalize viable but dysfunctional neuronal structures. Results were encouraging.     

Optimal open-loop desynchronization of neural oscillator populations

Deep brain stimulation (DBS) is an increasingly used medical treatment for various neurological disorders. While its mechanisms are not fully understood, experimental evidence suggests that through application of periodic electrical stimulation DBS may act to desynchronize pathologically synchronized populations of neurons resulting desirable changes to a larger brain circuit. However, the underlying mathematical mechanisms by which periodic stimulation can engender desynchronization in a coupled population of neurons is not well understood. In this work, a reduced phase-amplitude reduction framework is used to characterize the desynchronizing influence of periodic stimulation on a population of coupled oscillators. Subsequently, optimal control theory allows for the design of periodic, open-loop stimuli with the capacity to destabilize completely synchronized solutions while simultaneously stabilizing rotating block solutions. This framework exploits system nonlinearities in order to strategically modify unstable Floquet exponents. In the limit of weak neural coupling, it is shown that this method only requires information about the phase response curves of the individual neurons. The effects of noise and heterogeneity are also considered and numerical results are presented. This framework could ultimately be used to inform the design of more efficient deep brain stimulation waveforms for the treatment of neurological disease.

     

Neurostimulation and the minimally conscious state

Neurostimulation to restore cognitive and physical functions is an innovative and promising technique for treating patients with severe brain injury that has resulted in a minimally conscious state (MCS). The technique may involve electrical stimulation of the central thalamus, which has extensive projections to the cerebral cortex. Yet it is unclear whether an improvement in neurological functions would result in a net benefit for these patients. Quality-of-life measurements would be necessary to determine whether any benefit of neurostimulation outweighed any harm in their response to different degrees of cognitive and physical disability. These measures could also indicate whether the technique could be ethically justified and whether surrogates could give proxy consent to its use on brain-injured patients.     

Effects of vibrotactile stimulation on the control of muscle tone and movement facilitation in children with cerebral injury

Afferent signals from the muscle's proprioceptors play important role in the control of muscle tone and in the facilitation of movements. Peripheral afferent pathway enables the restoration of connections with supraspinal structures and so includes mechanism of synaptic inhibition in the performance of normal movement. Different sensory stimuli, as vibrotactile stimulation, excite muscle's proprioceptors which then send sensorimotor information via spinal cord. In this way afferent signals promote cortical control and modulation of movements. The goal of this study is to evaluate the effects of vibrotactile stimulation on the spasticity and motor performance in children with cerebral injury. Subjects included in this study were 13 children who were developing the classification of spastic cerebral palsy. For all children perinatal brain damage was documented by medical reports and neonatal brain ultrasound scan. At the mean age of 3 years and 6 months subject underwent the assessment of motor development by Gross Motor Function Measurement (GMFM-88). Gross Motor Classification System (GMFCS) has been used to classify functions of lower extremities. Therapeutic intervention was conducted once a week during 3 months. All subjects were stimulated with vibrotactile stimuli of 40Hz in duration of 20 minutes in order to reduce spasticity. After the ending of the treatment subjects underwent second assessment of motor performance and the classification of lower extremities functions. The results have shown that there was a significant improvement in motor performance, what has been seen in the facilitation of rotations, better postural trunk stability and head control and in greater selectivity of movements. Further randomized, control trial investigations with bigger sample and included spasm scale are needed to gain better insight in the role of vibrotactile stimulation in the facilitation of normal movements.     

Electrical stimulation as an adjunct to spinal fusion: a meta-analysis of controlled clinical trials

This study was a meta-analysis to examine whether electrical stimulation has a specific effect on spinal fusion. Little evidence exists on the efficacy of electrical stimulation for improving fusion rate of spinal fusion surgery. Using MEDLINE (1966-2000) and EMBASE (1985-1999), a search for articles was carried out using the Medical Subject Headings: (1) electric stimulation or electromagnetic fields, (2) spinal fusion, (3) controlled or clinical trial, and (4) human. Data were extracted from all the hit articles and additionally collected from appropriate journal lists. A total of five randomized controlled trials (RCT) on bones assessing healing of spinal fusion were identified and scored on methodological quality. All the identified studies reported positive findings, but the quality score of each trial showed wide flaws. Because of relatively homogenous subjects who had spine fusion and radiographic assessment from these studies, pooling of the data was able to be performed. Excluding one trial with the lowest score, the combined results of four trials, whose major endpoints were the success rate of the fusion, revealed a statistically significant effect of electrical stimulation with various techniques, but the selected trials still showed wide variation in view of stimulation modalities and treatment protocol. The pooled result of the studies in this review revealed the efficacy of electrical stimulation based on proved methodological quality. As problems on therapeutic modality and protocol remain, there is a further need for improvement in design to constitute acceptable proof and to establish treatment programs that better demonstrate electrical stimulation effects on spinal fusion.     

Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review

Background

Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment's potential effectiveness, safety and limitations.

Methods

We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.

Results

Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.

Conclusion

We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.     

Change of stretch reflex threshold in spasticity: effect of botulinum toxin injections

Spasticity is a disorder of hypertonus associated with neurological diseases, characterized by a decrease in stretch reflex threshold. Stretch reflex threshold of wrist flexors has been recorded in subjects affected by forearm spasticity due to acute neurological lesions, occurred from one to sixty-one months before. In all the subjects a decreased stretch reflex threshold was recorded and a negative correlation between stretch reflex threshold and time of the disease resulted. In five subjects affected by mild spasticity the velocity stretch reflex threshold was tested one-three months after stroke and then six months later. In three cases a further decrease in stretch reflex threshold was recorded. Sixteen subjects affected by heavy forearm spasticity (quantified by Ashworth scale), were treated with Botulinum toxin injections to reduce spasticity. Fourteen of 16 subjects were responsive to the antispastic therapy: a decrease of at least 1 point in the Ashworth scale was detected after the treatment. In all the responsive cases an increase of stretch reflex threshold was recorded. The results confirm that the stretch reflex threshold is decreased in spastic muscles; it decreases progressively in time after the acute lesion. In addition, these results demonstrate that the decreased stretch reflex threshold can be reversed with Botulinum toxin injections. It is known that Botulinum toxin reduce the presynaptic release of Acetylcholine of neuromuscular synapses, but there are experimental evidences that it acts even on spindle's fibres, decreasing the sensitivity of intrafusal muscle fibres. This effect explains how Botulinum toxin increases the stretch reflex threshold in spastic muscles.     

Electrostimulation: a future treatment option for patients with neurogenic urodynamic disorders?

This paper provides an overview of electrical stimulation of the nervous system as a treatment option for urodynamic dysfunction and of some of the recent results in this field. The set-up used in our studies for improved bladder filling in spinal cord injured patients by conditional stimulation of the dorsal penile/clitoral nerve is a highly efficient way to limit neurogenic detrusor overactivity and increase bladder capacity. Ongoing studies suggest that recording of bladder nerve activity is stable over time and may be a technique for chronic monitoring of bladder activity. Bladder emptying exploiting an anodal blocking technique permits bladder emptying without simultaneous urethral-perineal contraction, thus enabling a physiological voiding pattern in one continuous sequence. In patients with supraspinal lesions, deep brain electrical stimulation is established only as treatment for a subgroup of patients suffering from Parkinson's disease. Yet, with improved electrode designs and increased clinical experience and experimental results, probably other groups of patients may be candidates for deep brain stimulation. In our study in pigs there was a trend towards increased bladder capacity and compliance in response to stimulation, which is encouraging as several neurological diseases are accompanied by overactive bladder with reduced capacity.     

Model-based development of neuroprosthesis for paraplegic patients.

In paraplegic patients with upper motor neuron lesions the signal path from the central nervous system to the muscles is interrupted. Functional electrical stimulation applied to the lower motor neurons can replace the lacking signals. A so-called neuroprosthesis may be used to restore motor function in paraplegic patients on the basis of functional electrical stimulation. However, the control of multiple joints is difficult due to the complexity, nonlinearity, and time-variance of the system involved. Furthermore, effects such as muscle fatigue, spasticity, and limited force in the stimulated muscle further complicate the control task. Mathematical models of the human musculoskeletal system can support the development of neuroprosthesis. In this article a detailed overview of the existing work in the literature is given and two examples developed by the author are presented that give an insight into model-based development of neuroprosthesis for paraplegic patients. It is shown that modelling the musculoskeletal system can provide better understanding of muscular force production and movement coordination principles. Models can also be used to design and test stimulation patterns and feedback control strategies. Additionally, model components can be implemented in a controller to improve control performance. Eventually, the use of musculoskeletal models for neuroprosthesis design may help to avoid internal disturbances such as fatigue and optimize muscular force output. Furthermore, better controller quality can be obtained than in previous empirical approaches. In addition, the number of experimental tests to be performed with human subjects can be reduced. It is concluded that mathematical models play an increasing role in the development of reliable closed-loop controlled, lower extremity neuroprostheses.     

Comparison of techniques to determine human skeletal muscle voluntary activation

Determining volitional activation (VA) can provide insights on the cause of muscle weakness in orthopedic and neurological populations. Two electrical stimulation techniques are traditionally used to quantify VA: interpolation (IT) and superimposition (CAR). IT allows for a more accurate VA estimation, however it requires individuals to be stimulated twice, compared to once for CAR, and thus increases stimulation associated discomfort. To date, there is no agreement on what is the best practical technique for calculating quadriceps VA. This paper aims to address this problem by determining what reference force (i.e., using either peak force or force at the time of stimulation) and type of stimulation (train of pulses (burst), doublet, and twitch) is the best technique to use. Our findings showed that the IT with the force at the time of stimulation as a reference should be used to determine VA and that when a burst was used, the VA ratio computations were more accurate. Additionally, using a twitch with a 2 ms pulse duration produced reliable VA calculations and may be an acceptable alternative for pain-sensitive subjects. Accurate assessment of VA deficits can help clinicians design rehabilitation programs that are based on subject-specific strength impairments and are more effective.     

In Vitro and In Vivo Neuronal Electrotaxis: A Potential Mechanism for Restoration?

Electrical brain stimulation used to treat a variety of neurological and psychiatric diseases is entering a new period. The technique is well established and the potential complications are well known and generally manageable. Recent studies demonstrated that electrical fields (EFs) can enhance neuroplasticity-related processes. EFs applied in the physiological range induce migration of different neural cell types from different species in vitro. There are some evidences that also the speed and directedness of cell migration are enhanced by EFs. However, it is still unclear how electrical signals from the extracellular space are translated into intracellular actions resulting in the so-called electrotaxis phenomenon. Here, we aim to provide a comprehensive review of the data on responses of cells to electrical stimulation and the relation to functional recovery.     

Electrical Stimulation Promotes BDNF Expression in Spinal Cord Neurons Through Ca<Superscript>2+</Superscript>- and Erk-Dependent Signaling Pathways

Brief electrical stimulation has been shown to be effective in promoting neuronal regeneration following peripheral nerve injury. These effects are thought to be mediated largely by the upregulation of the expression of brain-derived neurotrophic factor (BDNF) in spinal cord neurons. However, the molecular mechanisms by which electrical stimulation can promote BDNF expression are not known. The mechanism involved in BDNF expression after electrical stimulation was explored in this study. Immunohistochemistry and Western blotting were used to test BDNF expression. Confocal microscopy was utilized to study intracellular Ca²⁺ volume. Immunohistochemistry and Western blotting confirmed that brief electrical stimulation increased BDNF expression in spinal cord neurons both in vivo and in vitro. Treatment of cultured neurons with nifedipine, an inhibitor of voltage-gated calcium channels, significantly reduced the BDNF increase produced by electrical stimulation, and an inhibitor of Erk completely abolished the effect of electrical stimulation. Levels of BDNF expression in the presence of the Erk inhibitor were lower that in unstimulated and untreated controls, indicating that Erk activation is required to maintain baseline levels of BDNF. Confocal microscopy using a Ca²⁺-sensitive fluorochrome revealed that electrical stimulation is accompanied by an increase in intracellular Ca²⁺ levels; the increase was partly blocked by nifedipine. These findings argue that electrical stimulation increases BDNF expression in spinal cord neurons by activating a Ca²⁺- and Erk-dependent signaling pathways.