Electrical stimulation in lower motoneuron lesions, from scientific evidence to clinical practice: a successful transition

Long pulse stimulation in its application in everyday clinical practice still represents a challenge for many therapists and clinicians. It is often unclear how the intervention setup, in particular the parameters pulse width, frequency and amplitude, can influence muscle morphology. In addition, the cause of damage to the lower motoneuron can have multiple reasons and is not anatomically located at the same site. Given the large heterogeneity, it is essential to know the current options and limitations in order to carry out a targeted treatment. A retrospective data analysis of n=128 patients, seen at the Swiss Paraplegic Centre (SPC) in 2022, shows a broad variability in manifestation of lower motoneuron damage. Treatment examples based on different causes of lower motoneuron damage are shown and corresponding stimulation programmes are assigned, as well as the expected results in terms of stimulation duration, volume and configuration

Medical image analysis and 3-d modeling to quantify changes and functional restoration in denervated muscle undergoing electrical stimulation treatment

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Neurophysiology of epidurally evoked spinal cord reflexes in clinically motor-complete posttraumatic spinal cord injury

Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input–output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity

Effects of sustained electrical stimulation on spasticity assessed by the pendulum test

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadNeuromodulation using electrical stimulation is able to enhance motor control of individuals suffering an upper motor neuron disorder. This work examined the effect of sustained electrical stimulation to modify spasticity in the leg muscles. We applied transcutaneous spinal cord stimulation with a pulse rate of 50 Hz for 30 min. The subjects were assessed before and after the intervention using in a pendulum test setup. The motion of the free swinging leg was acquired through video tracking and goniometer measurements. The quantification was done through the R2n index which shows consistency identifying the spasticity levels. In all incomplete SCI subjects having severe spasticity, the results show that electrical stimulation is effective to modify the increased muscle tone.Consejo Nacional de Ciencia y Tecnologí

Effects of sustained electrical stimulation on spasticity assessed by the pendulum test

Neuromodulation using electrical stimulation is able to enhance motor control of individuals suffering an upper motor neuron disorder. This work examined the effect of sustained electrical stimulation to modify spasticity in the leg muscles. We applied transcutaneous spinal cord stimulation with a pulse rate of 50 Hz for 30 min. The subjects were assessed before and after the intervention using in a pendulum test setup. The motion of the free swinging leg was acquired through video tracking and goniometer measurements. The quantification was done through the R2n index which shows consistency identifying the spasticity levels. In all incomplete SCI subjects having severe spasticity, the results show that electrical stimulation is effective to modify the increased muscle tone.Research funding: This work was supported by the Mexican Council of Research and Technology (CONACYT), Grant: 264528 (www.conacyt.mx) and; Landspitali – University Hospital science found (www.landspitali.is).Peer Reviewe

Long-term high-level exercise promotes muscle reinnervation with age.

The histologic features of aging muscle suggest that denervation contributes to atrophy, that immobility accelerates the process, and that routine exercise may protect against loss of motor units and muscle tissue. Here, we compared muscle biopsies from sedentary and physically active seniors and found that seniors with a long history of high-level recreational activity up to the time of muscle biopsy had 1) lower loss of muscle strength versus young men (32% loss in physically active vs 51% loss in sedentary seniors); 2) fewer small angulated (denervated) myofibers; 3) a higher percentage of fiber-type groups (reinnervated muscle fibers) that were almost exclusive of the slow type; and 4) sparse normal-size muscle fibers coexpressing fast and slow myosin heavy chains, which is not compatible with exercise-driven muscle-type transformation. The biopsies from the old physically active seniors varied from sparse fiber-type groupings to almost fully transformed muscle, suggesting that coexpressing fibers appear to fill gaps. Altogether, the data show that long-term physical activity promotes reinnervation of muscle fibers and suggest that decades of high-level exercise allow the body to adapt to age-related denervation by saving otherwise lost muscle fibers through selective recruitment to slow motor units. These effects on size and structure of myofibers may delay functional decline in late aging

PASS2 version 4: An update to the database of structure-based sequence alignments of structural domain superfamilies

Accurate structure-based sequence alignments of distantly related proteins are crucial in gaining insight about protein domains that belong to a superfamily. The PASS2 database provides alignments of proteins related at the superfamily level and are characterized by low sequence identity. We thus report an automated, updated version of the superfamily alignment database known as PASS2.4, consisting of 1961 superfamilies and 10 569 protein domains, which is in direct correspondence with SCOP (1.75) database. Database organization, improved methods for efficient structure-based sequence alignments and the analysis of extreme distantly related proteins within superfamilies formed the focus of this update. Alignment of family-specific functional residues can be realized using such alignments and is shown using one superfamily as an example. The database of alignments and other related features can be accessed at http://caps.ncbs.res.in/pass2/

Cell stress is related to re-localization of Argonaute 2 and to decreased RNA interference in human cells

Various kinds of stress on human cells induce the formation of endogenous stress granules (SGs). Human Argonaute 2 (hAgo2), the catalytic core component of the RNA-induced silencing complex (RISC), can be recruited to SGs as well as P-bodies (PBs) indicating that the dynamic intracellular distribution of hAgo2 in SGs, in PBs or at other sub-cellular sites could be related to the efficiency of the RNA interference (RNAi) machinery. Here, we studied the influence of heat shock, sodium arsenite (NaAsO2), cycloheximide (CHX) and LipofectamineTM 2000-mediated transfection of phosphorothioate (PS)-modified oligonucleotides (ON) on the intracellular localization of hAgo2 and the efficiency of RNAi