Maladaptive changes in motor unit behavior and neuromuscular control, associated with spasticity rather than weakness, are well documented. Evidence from animal models, histologic analyses, and high-density surface electromyography (HDsEMG) studies in individuals with chronic stroke indicates a reduction in the number of functional motor units in spastic muscles. Additionally, there is a persistent reduction in the voluntary activation of remaining motor units, leading to muscle weakness and impaired selective motor control. These deficits are primarily attributable to upper motor neuron lesions and are further compounded by secondary effects of immobilization and disuse. ^,

Spastic-paretic muscles also demonstrate impaired modulation of motor unit firing rates during voluntary contraction, often exhibiting early saturation or plateauing of firing frequencies despite increasing force demands. This abnormal firing behavior reflects disrupted descending drive and altered spinal circuitry. Additionally, an increased incidence of spontaneous motor unit firing at rest is observed in spastic muscles, likely due to persistent low-level excitatory synaptic input and changes in intrinsic motoneuron membrane properties, rather than enhanced excitability alone. ^,

Impaired inhibitory control further contributes to neuromuscular dysfunction. Specifically, reduced inhibition of motoneurons by sensory pathways leads to hyperexcitability of stretch reflexes and excessive co-contraction of antagonist muscles. This is particularly evident in conditions such as cerebral palsy (CP) and post-stroke spasticity, where decreased inhibitory postsynaptic potentials are thought to underlie increased muscle tone and impaired motor coordination. ^,,

HDsEMG studies have also revealed that motor unit recruitment in spastic muscles tends to be highly synchronous and spatially non-uniform. This pattern results in elevated muscle activation but diminished complexity and adaptability of motor output, further limiting functional performance. ^,

Collectively, these neuromuscular adaptations, including reduced motor unit number, impaired firing behavior, spontaneous activity, loss of inhibitory control, and abnormal recruitment patterns, contribute to decreased strength and impaired neuromuscular control in spastic paresis.

Spastic muscles undergo a range of adaptive structural changes, including muscle fiber loss, fiber type shifts, increased stiffness, variable sarcomere length (shortened or elongated depending on context), reduced capillarization, greater fiber size variability, and extensive ECM remodeling characterized by increased collagen deposition. ^,,,,,,,, A consistent finding is a shift in muscle fiber type composition, typically marked by an increased proportion of fast-twitch (type IIx) fibers and a reduction in slow-twitch (type I) fibers. This pattern has been observed in both spinal cord injury and CP, and is associated with reduced oxidative capacity and increased fatigability. ^, Concurrently, capillary density is diminished, with fewer capillaries per fiber and per tissue area, further exacerbating fatigue. ^,,

Spastic muscle fibers are frequently shorter and stiffer than those in non-spastic muscles, characterized by reduced resting sarcomere lengths and an increased elastic modulus at the single-fiber level. Paradoxically, some studies in children with CP have reported increased in vivo sarcomere lengths, suggesting context-dependent variability. These alterations, when combined with extensive ECM remodeling, contribute to elevated passive muscle stiffness. ^,, A key structural adaptation observed in spastic muscles is the presence of fewer sarcomeres in series, which further amplifies stiffness and increases the risk of contracture, particularly in the context of ECM expansion and fibrosis. ^,,,,,

These alterations collectively result in muscle atrophy, as evidenced by a reduction in muscle mass and cross-sectional area in spastic muscles. They likely contribute to the high prevalence of sarcopenia in stroke survivors with spasticity. While spastic-paretic muscle shares some features with sarcopenia, including satellite cell dysfunction, mitochondrial impairment, and decreased protein synthesis, its pathophysiology differs. Age-related sarcopenia involves preferential loss of type II fibers and a relative increase in type I fiber proportion, with less prominent ECM expansion and passive stiffness. ^,,,,

Interestingly, spasticity may help preserve muscle mass in some instances, particularly in the lower limbs, due to the sustained involuntary muscle activation observed after stroke and spinal cord injury. Nevertheless, this preservation does not prevent qualitative impairments, including increased fatigability and altered fiber type distribution. ^,,,

Loss of muscle fibers is accompanied by ECM expansion and remodeling in spastic muscles. These changes include increased collagen deposition, altered collagen architecture, thickening of connective tissue layers, reduced satellite cell numbers, pro-inflammatory gene expression, and hyaluronan accumulation. ^,,,,,

The ECM of muscles is composed of collagens, glycoproteins, proteoglycans, and elastin. Collagen, predominantly types I and III, forms the intramuscular connective tissue (IMCT) that constitutes the central fibrous components of the ECM. IMCT is a part of the fascial system that is composed of the epimysium (surrounds the entire muscle), the perimysium (bundles groups of muscle fibers), and the endomysium (surrounds the muscle fiber). Fascia is a continuous, web-like structure that connects everything from the skin to the muscle to the bone. Fascia provides a scaffolding support to the body, allowing muscles and other tissues to move and function properly. Irregularly arranged collagen fibers provide mechanical stability by resisting stress from multiple directions. Spastic muscles consistently show increased deposition of collagen, particularly type I collagen within the endomysium and the perimysium. In spastic muscles, collagen fibers become more aligned and cross-linked, especially during muscle stretching, further increasing passive stiffness and reducing joint range of motion. Comparison of muscle biopsies from spastic CP and normal muscle showed thickened fascia primarily involving the perimysium or the endomysium in the spastic muscles. The degree of collagen accumulation correlates with the severity of spasticity and functional impairment. ^,, In a recent study, the fascia layer overlying muscles, assessed by quantitative B-mode ultrasound imaging, was thicker in all the spastic muscles tested in the paretic side as compared to those on the contralateral side of chronic stroke survivors.

A marked reduction in satellite cell populations and impaired muscle growth and regeneration in spastic muscles potentially exacerbate ECM expansion. ^, Furthermore, there is upregulation of proinflammatory cytokines and genes involved in ECM production, which may drive ongoing fibrosis and tissue remodeling. Hyaluronan is the primary component in the ECM and functions to lubricate the muscle fiber gliding system during muscle force transmission. The normal turnover of the ECM decreases after immobilization or spastic paresis, thus increasing its concentration and the molecular weight and macromolecular crowding within and between muscular compartments ^,

Increased hyaluronan crowding and accumulation within the ECM has been implicated in raising tissue viscosity and potentiating muscle stiffness, possibly further promoting fibrosis and contracture.

Tendon contractures occur when tendons rest in a tightened and shortened joint position. Histology studies showed that tendons from spastic CP subjects contained an increased content of collagen and glycosaminoglycans as compared with those from healthy subjects. The results suggest that tendons of individuals with spastic CP underwent chronic and repetitive loading, inducing ECM remodeling as an adaptive response to increased functional demand. A combined ultrasound–biomechanical assessment showed negatively correlated deficits in changes in muscle fascicles and the Achilles tendon in persons with chronic stroke. ^, The spastic paretic side showed decreased fascicle length and increased fascicular stiffness in gastrocnemius and soleus muscles. In contrast, the Achilles tendon on the impaired side exhibited increased tendon length and decreased tendon stiffness compared to the contralateral side. However, contracture can occur independently of spasticity in stroke survivors, and may actually potentiate spasticity.

BoNT inhibits presynaptic acetylcholine release at the neuromuscular junction via a complex process, resulting in post-synaptic denervation effects. ^,, BoNT chemodenervation leads to a significant reduction in muscle overactivity and spasticity. It also subsequently causes axonal sprouting and the development of extrajunctional acetylcholine receptors. Over time, reinnervation occurs, leading to the remodeling of motor units. Specifically, there is an increase in motor unit action potential amplitude and a reduction in motor unit territory, indicating the emergence of newly innervated muscle fibers and an altered motor unit structure. This remodeling is a direct consequence of the denervation–reinnervation process triggered by BoNT. ^,

Furthermore, BoNT-related chemodenervation causes other muscular changes in spastic muscles as well. In both animal and human studies, molecular changes associated with this chemical denervation include altered expression of muscle-specific microRNAs and upregulation of atrophy-related genes. ^,,, Muscular adaptation following BoNT injection consists of a shift toward more oxidative (slow-type) fibers and increased mitochondrial enzyme activity, which may improve endurance capacity in some settings, but overall force-generating capacity is reduced due to fiber loss and atrophy.

BoNT injections cause loss of muscle fibers in patients with spasticity and paresis, leading to muscle atrophy. The atrophic changes are characterized by a reduction in muscle cross-sectional area, loss of muscle fibers, in some cases, increased intramuscular fat and connective tissue. These effects are observed within weeks to months after injection and may persist. ^,,, In animal models, recovery of muscle mass and function occurs over time, mediated by neuromuscular junction remodeling and myogenesis, but the process is incomplete and may not fully restore pre-injection muscle structure, particularly with repeated injections. ^, In children with spastic CP and adults with chronic stroke, reductions in muscle volume and contractile material have been documented after BoNT injection, and repeated or high-dose injections may impair full recovery of muscle mass and function.

It is important to emphasize that the degree of additional muscle loss attributable to BoNT, beyond that caused by spasticity and paresis alone, may be modest in the short term. Repeated BoNT injections can cause cumulative effects and increase the risk of clinically significant muscle atrophy and sarcopenia over time. ^,,,, Animal models confirm that repeated injections result in sustained reductions in muscle mass, contractile material, and strength, with incomplete recovery even after 6 months, and replacement of muscle tissue by fat. ^,, Long-term imaging and histologic studies confirmed these findings in pediatric populations. ^, These changes are not fully reversible, and the cumulative effect of repeated injections may lead to progressive muscle weakness and increased intramuscular fat, both of which are key features of sarcopenia. ^, The risk is further heightened in the context of underlying paresis and disuse.

There is no evidence that any one formulation (onabotulinumtoxinA, abobotulinumtoxinA, or incobotulinumtoxinA) is superior in preserving muscle structure or reducing sarcopenia risk when best practices for interval timing and rehabilitation are followed. ^,,, The risk of persistent muscle atrophy and impaired recovery increases with shorter injection intervals (<3–6 months) and in the absence of structured rehabilitation protocols. ^,,, Longer intervals between repeated BoNT injections allow for greater muscle recovery and reduce the risk of cumulative muscle atrophy. In pediatric populations, a 6 month interval is associated with reduced cross-sectional muscle growth, and the literature suggests that reinjections should be postponed at least beyond 6 months to minimize long-term muscle loss. ^,, Clinical studies in both adults and children with spastic paresis show that symptom relief from BoNT often lasts at least 12 to 16 weeks, and a significant proportion of patients do not require retreatment before 16 to 28 weeks. Shorter intervals (<12 weeks) are not recommended, as they increase the risk of cumulative muscle atrophy and impaired muscle growth. ^,

Rehabilitation protocols that combine early, intensive, and multimodal interventions, such as stretching, strengthening, task-oriented exercises, and neuromuscular electrical stimulation, between BoNT injection intervals can provide additional benefit over BoNT alone in improving joint mobility and limb function. However, the magnitude of effect is modest and study heterogeneity limits definitive conclusions. ^, They are also associated with improved muscle recovery and a reduced risk of muscle atrophy and sarcopenia. Initiating rehabilitation within the first week after injection is widely supported by expert consensus, with stretching and electrical stimulation recommended to enhance the effects of BoNT and promote muscle preservation. ^,,

Phenol acts as a neurolytic agent by denaturing proteins and causing chemical neurolysis, resulting in axonal degeneration (Wallerian degeneration) of the targeted nerve. This neurolysis blocks neural inputs and can lead to muscle atrophy and, in some cases, direct muscle necrosis if phenol is injected intramuscularly or if high concentrations are used. Both nerve and muscle tissues exhibit evidence of regeneration through reinnervation or collateral sprouting, which is a process of motor unit remodeling. Histologically, axonal regeneration is typically delayed and is first observed after 2 weeks. Regeneration in both nerve and muscle is well established by 2 months, and almost complete in 3 months, but residual morphologic changes can persist for up to 6 months or longer. ^,,, These histologic findings are consistent with the clinical observation that the peak effects are observed about 10 days to 2 weeks after phenol neurolysis, and the effects last approximately 6 months. ^,

Partial neuromuscular recovery occurs after phenol neurolysis and BoNT chemodenervation. Phenol’s effects are more likely to be associated with nerve degeneration and subsequent reinnervation, while BoNT primarily induces reversible chemical denervation at the neuromuscular junction. Electrophysiological studies confirm that phenol neurolysis reduces the amplitude of the M response, reflecting a direct effect on alpha motor fibers and subsequent changes in motor unit structure and function, which is distinct from the presynaptic blockade of acetylcholine release seen with BoNT. ^,,

Due to ECM expansion, immobilization, and spastic paresis, the normal turnover of hyaluronan in the ECM decreases, subsequently increasing its concentration and the molecular weight and macromolecular crowding within and between muscular compartments in spastic muscles. ^, These changes can increase fluid viscosity and decrease lubrication between muscle fibers and their compartments. Such change may be perceived by the stroke survivor as stiffness. Hyaluronidase is an enzyme that hydrolyzes hyaluronan, a macromolecular component of muscle stiffness, thus specifically targeting this component of muscle stiffness. Raghavan and colleagues reported that hyaluronan in the ECM was significantly higher in spastic muscles in stroke survivors as compared with those in healthy controls. They also observed that passive resistance was significantly reduced and the range of motion of treated joints was significantly increased in stroke survivors after hyaluronidase injections compared to baseline. ^, These results support the hyaluronan hypothesis of muscle stiffness. More studies are needed to confirm these findings and to investigate how this treatment can be combined with other interventions, such as chemodenervation, to optimize the outcome of spasticity management.

Dry needling involves inserting thin, solid needles into the skin and muscle at trigger points to elicit a local twitch response. It is commonly used to treat musculoskeletal pain with myofascial trigger points. It has also been used to reduce spasticity because of its direct mechanical effects and associated neuromodulatory effects. Dry needling may reduce muscle thickness and stiffness, likely by mechanically disrupting abnormal endplate activity and altering local muscle fiber and connective tissue properties; however, these effects are modest and not sustained beyond several weeks. Dry needling can further modulate spinal reflexes by increasing reciprocal inhibition and reducing reflex torque, which transiently decreases motoneuron excitability and muscle tone. Neurophysiological studies indicate that dry needling can enhance inhibition at the spinal level without significantly altering the amplitude of the excitatory H-reflex. This leads to immediate but temporary improvements in range of motion and reductions in spasticity. ^,

Dry needling has been evaluated in several systematic reviews and randomized controlled trials for chronic spasticity, primarily following stroke. Evidence consistently demonstrates that dry needling is effective in reducing muscle tone (as measured by the Modified Ashworth Scale) and improving passive range of motion (ROM) in the short term. ^, Some studies report additional benefits when dry needling is combined with neurorehabilitation, including reductions in muscle thickness and reflex torque, suggesting a potential impact on both neural and non-neural adaptations. However, the effects of dry needling are generally short-lived, with most studies showing no sustained benefit beyond 4 weeks. There is significant heterogeneity in protocols, treated muscles, and outcome measures, and most studies are small and of limited duration, highlighting the need for more robust, long-term trials. ^,

Minimally invasive surgical techniques, such as percutaneous myofasciotomy or needle tenotomy, have been employed to release contracted fascia or tendons in patients with chronic spasticity. Recently, a case report described the mechanical disruption of thickened fascia overlaying spastic biceps muscles using PNF, resulting in immediate reduction of elbow flexor spasticity and improved voluntary movement ( Fig. 2 ).

This was a 62-year-old man with right hemiparesis and spasticity from a stroke 3 years ago. He received multiple rounds of BoNT injections to his right elbow flexors. He received percutaneous needle fasciotomy before repeated BoNT injections. During the ultrasound-guided procedure, the needle was inserted reached to the thickest part of the fascia overlaying the spastic biceps muscle ( A ). The fascia was broken down mechanically about 1 cm horizontally at its tightest and thickest part. Immediately after the procedure, MAS of elbow flexors decreased from 2 to 1. He was able to voluntarily extend his elbow further ( C vs D ). Comparison of fascia overlaying the biceps muscles from ultrasound images of spastic biceps muscles ( A ) and of contralateral non-spastic biceps muscles ( B ). Arrowhead , facia layer; Arrow, depath of the biceps muscle.

Unlike conventional spasticity treatments such as chemodenervation, which targets the neuromuscular junction, or neurolysis targeting nerves, this case highlights a potential role of fascia in the pathophysiology and management of spasticity. Fascia is richly innervated with various sensory receptors and shares innervation with adjacent tissues, such as muscle fibers and spindles, thereby creating a convergence of sensory input. Muscle biopsy comparisons between spastic muscles in individuals with CP and normal muscle tissue have revealed fascia thickening, primarily involving the perimysium and endomysium. Quantitative ultrasound assessment also shows significantly increased thickness of fascia layer overlaying spastic muscles than the contralateral muscles in stroke survivors. It is plausible that PNF disrupts sensory input from the fascia to the spinal reflex pathways, thereby contributing to the reduction of spasticity. On the other hand, mechanical disruption of a small portion fascia is not likely to reduce spasticity ; it may play a role in improving range of motion. This hypothesis is further supported by findings that manual fascial manipulation and release can effectively alleviate spasticity in both upper and lower limbs in stroke patients. The significance of this observation is that it provides a novel approach to managing spasticity. It can be easily integrated into a multimodal management approach. Further studies are needed to validate this observation and better understand its mechanisms and efficacy.