Layout 1 Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 Cerebral stroke, also known as cerebrovascular accident, includes cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage. With the development of an older society and the improvement of medical treatments, the death rate of stroke has gradually decreased, instead, the disability rate has increased year by year. Clonus is a form of hypertonia, often manifested as velocity-dependent stretch hyperreflexes accompanied by tendon twitching, and is one of the manifestations of upper motor neuron syn- drome.1 The prevalence of post-stroke spasticity is 25.3%, and as high as 39.5% in hemiplegic patients, among which 9.4% of hemiplegic patients have severe or disabling symp- toms.2 The moderation of the spasticity is conducive to pos- ture maintenance and a certain extent beneficial to rehabili- tation. Whereas, excessive spasticity will lead to the occurrence of abnormal movement patterns and pain, which seriously limit the improvement of patients’ daily living ac- tivities and prognosis. The common clinical presentation of spasticity in stroke pa- tients with hemiplegia is the lower extremity extensor pat- tern. The manifestations are straightening of the knee joint, foot drop, and pronation. The triceps surae is formed by the medical before lateral gastrocnemius and the soleus mus- cles. The gastrocnemius and soleus muscles work together Abstract Lower limb spasticity and clonus are common sequelae after cerebral stroke. An important part of their etiopathogenesis has been related to the peripheral component of spasticity. Rheological properties of the tissues seem to be involved. Several studies highlighted anatomical and functional changes in the connective structures. The fasciae might be implicated in the pathological process. Thus, this study intends to investigate the effect of the Fascial Manipulation (FM) technique on triceps surae in stroke patients through a clinical randomized controlled trial, to provide a reference for clinical treatment of lower limb spasticity and ankle clonus. A total of 40 patients with post- stroke ankle clonus were selected and divided into a control group and an observation group by random number table method, with 20 cases in each group. Both groups received conventional rehabilitation therapy, while the FM group received Fascial Manipulation based on conventional rehabilitation therapy. Before the first treatment and after 3 weeks of treatment, the Comprehensive Spasticity Scale (CSS), the Passive Range Of Motion (PROM), the simplified Fugl-Meyer motor function score (FMA), and the Modified Ashworth Scale (MAS) were used to assess the degree of ankle clonus, ankle passive range of motion, and lower limb motor function of the two groups of patients. Before treatment, there was no statistically significant difference between the control group and the FM group in terms of CSS, PROM, FMA, and MAS of the affected lower limbs (P>0.05). After 3 weeks of treatment, the CSS and MAS of the affected lower limbs in the control group and FM group decreased, while PROM and FMA increased compared to pre-treatment evaluation, with statistically significant differences (P<0.05). Moreover, the FM group showed a statistically significant decrease in CSS and MAS, as well as an increase in PROM and FMA, compared to the control group (P<0.05). Conclusions: Fascial manipulation in addition to conventional therapy can effectively reduce spasticity and ankle clonus in stroke patients in a short time, and improve the passive range of motion of the ankle joint and the function of lower limbs. Key Words: stroke; spasticity; fascia; peripheral component; clonus; triceps spasm. Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 The effect of fascial manipulation therapy on lower limb spasticity and ankle clonus in stroke patients Wenyan Li,1 Xin Liu,1 Yinghua Wen,1 Junying Wu,1 Federico Giordani,2 Carla Stecco3 1First Hospital of Shanxi Medical University, TaiYuan, China; 2Villa Rosa Neurological Rehabilitation Hospital, APSS Trento, Italy; 3Neuroscience Department, University of Padova, Padova, Italy. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. - 12 - Non -co mmerc ial us e o nly Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 to flex the foot. Stroke patients with hemiplegia have leg triceps hypertonia, clonus, and abnormal gait, which in- creases the risk of falling3 and seriously affects the walking function. Therefore, effective treatment of calf triceps spas- ticity is essential. At present, the treatment methods for tri- ceps spasticity of the lower leg mainly include stretch, radial or focused extracorporeal shock wave therapy, neu- romuscular electrical stimulation and other physical factor therapy, wearing ankle and foot orthotics, oral drug therapy, local and intrasheath drug injection therapy, and surgical treatment.4 Therefore, treatments targeting spasticity that are more economical, effective, and noninvasive with fewer side effects still need to be studied. Recently, some papers have highlighted the possible involvement of the muscular fascia in spasticity, and some clinical trials suggest that a change in the fascial viscosity can decrease the muscular symptoms in post-stroke patients. The hypothesis is consis- tent with recent literature that proposes a role for peripheral tissue in the development of spasticity, in particular, the in- crease in viscoelastic properties of tissue.5,6 This study intends to explore the effectiveness of Fascial Manipulation on the triceps muscle of the calf in stroke pa- tients to reduce spasticity. It aims to provide a new approach for lower limb spasticity. Materials and Methods Participants Patients enrollment A total of 40 patients with post-stroke triceps spasms were selected from October 2020 to December 2021 in the De- partment of Rehabilitation Medicine, the First Hospital of Shanxi Medical University. All the participants were in line with the stroke diagnosis points formulated by the Fourth Conference on Cerebrovascular Diseases of the Chinese Medical Association.7 This study was approved by the Ethics Committee of the First Hospital of Shanxi Medical University, and all the patients and their families agreed to join the study and signed informed consent. Inclusion criteria i) Cerebral infarction or cerebral hemorrhage was dia- gnosed by head CT or MRI; ii) First onset, stable condition, understanding and cooperative treatment, course of disease 2 weeks to 6 months; iii) There was significant triceps surae spasticity, the Composite Spasticity Scale (CSS) was ≥7 and the Modified Ashworth Scale(MAS)≤level 3. Exclusion criteria i) Unstable vital signs; ii) Severe cognitive dysfunction; iii) Limited ankle joint activity, or local skin damage, infection; iv) Have coagulation dysfunction or thrombosis; iv) Have received other antispasmodic treatment in addition to con- ventional rehabilitation treatment. Experimental grouping This blinded randomized controlled trial was approved by the First Affiliated Hospital of Shanxi Medical University ethics committee. Forty patients with triceps spasms after stroke were selected and divided into two groups by random number table method: control group and FM group, with 20 cases in each group. Both groups received conventional rehabilitation therapy, and the FM group was treated with Stecco Fascia ManipulationR based on conventional re- habilitation therapy. Stecco Fascia ManipulationR for 3 weeks, twice a week, 30 minutes a time. In addition to blinding the subjects, we blinded the clinicians and the scale evaluators. Treatment methods i) Conventional rehabilitation therapy includes good limb placement, stretching training, physical factor therapy, balance function training, sitting and standing transfer training, muscle strength training, range of motion train- ing, walking training, etc. The treatment duration is 3 weeks, 5 times per week, 40 minutes per time. The con- ventional rehabilitation therapy group was treated by the same physician. ii) Stecco Fascia ManipulationR: Accord- ing to the Stecco Fascia ManipulationR assessment, dia- gnosis, and treatment system including movement and palpation examination, comprehensive evaluation, and scoring were performed. Finally, the selected myofascial chains were treated. Under the premise of fully exposing the skin of the calf and foot on the affected side, the ther- apist pressed and rubbed CC through the knuckles, finger abdomen, elbow joints, etc., and ended the treatment at this point when the patient reported that the pain was halved or the tissues gliding restored. Initial myofascial points were selected by a Fascia spe- cialized Rehabilitation physician using a specific assess- ment methodology—Fascial Manipulation8 involving clinical examination by movement and palpatory verifi- cations of specific points termed Centers of Coordination (CC). The rehabilitation specialist is certified as a Fascial Manipulation Specialist. The experts need training to ob- tain a fascia certification. A CC corresponded to the con- vergence of vectorial forces, into the deep fascia, generated by mono and biarticular motor units moving a joint in a specific direction. Palpation evaluation of these points included patient pain rate, radiation, and the pres- ence of tissue stiffness.8 The stiffness perceived by the physician. Dysfunctional segments were identified based on palpation evaluation and a hypothesis-driven differen- tial by clinical history. The CC selected for treatment and belonging to the selected dysfunctional segments were compared to the muscles localized by standard dystonia assessment (Figure 1). The location and operation methods of CC: i) IR-TA-CC: inside 1/3 of the middle leg, on the fascia of the tibial pos- terior muscle: the patient was supine with the inner leg facing upward; the therapist is located on the same side of the treatment point and uses the knuckles or elbows; ii) ER-TA-CC: peroneal longus and brevis: the patient was in a lateral position; the therapist is located on the same side of the treatment point and uses the elbow joint, or is located opposite the treatment point and uses the elbow joint; iii) RE-TA-CC: on the fascia of the triceps surae: the patient was placed in the prone position; the therapist - 13 - Non -co mmerc ial us e o nly is located on the same side of the treatment site and uses the elbow joint; iv) ME-TA-CC: the medial head of the gastrocnemius muscle is close to the tendon: the patient was placed in the prone position; the therapist is located on the same side of the treatment site and uses the elbow joint; v) AN-PE-CC: between the first and second pha- langes, on the fascia of the extensor hallucis brevis mus- cle; the Patient was placed in the prone position and bent his knee; the therapist is located on the same side of the treatment point and uses the finger joint; vi) LA-PE-CC: dorsal side of the 2nd and 3rd interosseous muscles; the Patient was placed in the prone position and bent his knee; the therapist is located on the same side of the treatment point and uses the finger joint; each point was treated for 5 minutes, the treatment lasted 30 minutes and was per- formed twice a week for a total of 3 weeks before conven- tional rehabilitation therapy. Evaluation method The same rehabilitation physician evaluated the two groups of patients before the first treatment and 3 weeks after treat- ment, respectively. The physician does not know the differ- ent groups. The specific evaluation methods were as follows. CSS CSS9 was used to reflect the changes in the degree of triceps spasm before and after treatment in the two groups. CSS includes three aspects of evaluation: muscle tension of calf triceps: 0, 2, 4, 6, and 8 points are assigned according to the size of muscle tension. The greater the muscle tension, the higher the score; Achilles tendon reflexes: from no reflexes to hyperreflexes, rated 0 to 4; Ankle clonus: On a scale of 1 to 4, the larger the score, the more severe the ankle clonus. The sum of the three rating scores is the final CSS score, CSS≥7 points is spasticity, the higher the CSS score, the more severe the spasticity. Passive range of motion Passive Range of Motion (PROM)10 was used to measure the passive range of motion of the ankle. The patient was in the supine or seated position, and the rehabilitation phys- ician measured the maximum passive dorsiflexion and plantarflexion Angle of the affected ankle joint with the help of a protractor. The sum of the two was PROM. A larger PROM indicates better ankle motion and less limitation of motion. Fugl-Meyer motor function score Simplified Fugl-Meyer motor function score (FMA)11,12 was used to evaluate the motor function of the affected lower extremity. The total score was 34 points. The higher the score was, the better the motor function of the affected lower extremity was. Modified Ashworth Scale (MAS) Level 0: No increase in muscle tone, scored 0; Level I: Mild increase in muscle tension, with the affected part passively flexing and extending, the end of the range of motion sud- denly getting stuck and showing minimal resistance, scored 1; Level I+: Mild increase in muscle tension. During pas- sive flexion and extension, 50% of the joint’s range of mo- tion suddenly gets stuck. When continuing to conduct joint motion examination to the end, there is always a small re- sistance, scored 2; Level II: Muscle tension increases sig- nificantly, and resistance increases significantly when moving through most of the range of motion of the joint. However, the affected part can still move more easily, scored 3; Level III: Severe increase in muscle tone, diffi- culty in passive activity examination, scored 4; Level IV: Stiffness, inability to bend or extend the affected part, scored 5.12 Statistical analyses SPSS 25.0 software was used to analyze the data. Count- ing data were tested by chi-square test. Measurement data were expressed as mean ± standard deviation (X±S), paired sample t-test was used for intra-group comparison, and independent sample t-test was used for inter-group comparison. P<0.05 indicated a statistically significant difference. Results General information The gender, age, course of disease, and lesion nature of the two groups were compared, and the difference was not sta- tistically significant (P>0.05), which was comparable, as shown in Table 1. Evaluation of clinical efficacy Comparison of CSS before and after treatment Before treatment, there was no significant difference in CSS between the two groups (P>0.05). After treatment, the CSS in the two groups was lower than that before treatment, the difference was statistically significant (P < 0.05). The re- duction in the FM group was higher, compared with the control group, and the difference was statistically significant (P < 0.05), (Table 2). Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 - 14 - Figure 1. The CCs were selected for treatment under standard dystonia assessment. Non -co mmerc ial us e o nly Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 PROM comparison before and after treatment Before treatment, there was no significant difference in PROM between the two groups (P>0.05). After treatment, the PROM of the two groups was increased compared with that before treatment, and the difference was statistically significant (P<0.05; Figure 2). The increase of the FM group was more obvious, compared with the control group, and the difference was statistically significant (P<0.05; Table 3). Comparison of lower limb FMA before and after treatment Before treatment, there was no statistically significant dif- ference in lower limb FMA between the two groups (P>0.05); after treatment, in intra-group comparison, the lower limb FMA of the two groups was higher than that be- fore treatment, the difference was statistically significant(P<0.05), and the increase was more obvious in the FM group, compared with the control group, the differ- ence was statistically significant (P<0.05; Table 4). Comparison of MAS before and after treatment Before treatment, there was no significant difference in MAS between the two groups (P>0.05). After treatment, the MAS in the two groups was lower than that before treat- ment, the difference was statistically significant (P<0.05), and the reduction in the FM group was more obvious, com- pared with the control group, the difference was statistically significant (P<0.01; Table 5). Discussion Spasticity is a form of hypertonia, often occurring in stroke patients. Although there is much research on the mechanism of spasticity after stroke, the specific pathophysiological mechanism is still not completely clear. At present, it is be- lieved that the mechanism of spasticity after stroke mainly includes neural mechanisms and peripheral mechanisms. The neural mechanism is mainly manifested in abnormal descending regulation and abnormal intraspinal processing - 15 - Table 1. Comparison of general data between the two groups (X±S). Group Total Sex Age (year) Duration of stroke Stroke type Patients Male Female (`X±S) (days) (`X±S) Infarct hemorrhage Control group 20 12 8 55.75±13.08 53.21±18.22 11 9 FM Group 20 10 10 52.63±13.73 50.80±13.32 13 7 Table 2. Comparison of CSS before and after treatment between the two groups (X±S). Group Number Pre-treatment Post-treatment t P Control group 20 12.25±1.33 11.50±1.23a 3.290 0.004 FM Group 20 12.05±1.23 10.70±1.12ab 10.283 0.000 t 0.492 2.138 P 0.625 0.039 a, ???????; b, ??????????. Table 3. Comparison of PROM before and after treatment between 2 groups (X±S). Group Number Pre-treatment Post-treatment t P Control group 20 44.56±7.59 49.68±9.69a -3.104 0.006 FM Group 20 47.59±11.16 64.51±11.77ab -5.140 0.000 t -1.005 -4.347 P 0.321 0.000 Non -co mmerc ial us e o nly Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 function. Over-excitation of α-motor neurons is the main manifestation of spinal cord changes in stroke patients with spasticity.13 The peripheral mechanism is mainly the change of muscle mechanical properties,14 that is, the inherent prop- erties and muscle metabolism and function of the tissues that make up muscles, tendons, joints, and other structures. To further explore the mechanism of spasticity after stroke, Mirbagheri et al.15 found in an observation of the mechan- ical properties of elbows of patients with muscle spasms after stroke that the spasticity mechanism gradually tran- sitioned over time from neurological factors to peripheral mediated factors. In a study on the number of motor units of the hypothenar muscle in the hands of patients with cere- bral infarction, Arasaki et al.16 found that the tissue structure of the muscle changed as early as 4 hours after cerebral in- farction. Compared with normal muscles, spastic muscles showed increased stiffness after stroke.17 At the same time, the increased stiffness of the muscle will further aggravate the spasticity of the limb. As for endomysium and perimy- sium, the collagen densities in connective tissue increases. Thus, injured muscles trended to become stiffer with a more linear behavior and a larger viscous component.18 The primary lesion leading to spasticity lies within the cen- tral nervous system, but the connective tissue in patients with spasticity is also dramatically altered because of para- lysis and the ensuing immobilization. Antonio Stecco19 argues that connective tissue alterations begin a vicious cir- cle composed of three phases: i) an increase in the viscosity - 16 - Figure 2. Comparison of various indexes before and after treatment between 2 groups. Non -co mmerc ial us e o nly Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 of the extra-cellular matrix leading to active muscle stiff- ness; ii) exacerbation of neurally mediated reflex mech- anisms due to subclinical contractures affecting the threshold of muscle spindle activation; iii) fibrosis due to collagen deposition and an increase in passive muscle stiff- ness. Fibrosis leads to a further increase in extracellular ma- trix viscosity in the surrounding areas re-starting the circle. These peripheral mechanisms contribute to abnormal pos- tural adaptation, and further disuse and disability. Thus, re- storing normal connective tissue architecture and tissue gliding mechanisms might help interrupt the vicious circle. Fascia is a dense, irregular, and malleable connective tissue that penetrates the human body to form a continuous three- dimensional structural support matrix of the whole body, which can adjust mechanical, thermal, and metabolic stress, and can be restored to its physiological state through exter- nal manipulative treatment.20 The deep fascia refers to all the ordered, dense, fibrous layers that interact with the mus- cles, connecting different structures of the musculoskeletal system and transmitting muscle power far away.7 Located at the junction of the deep fascia and the muscle surface, Hyaluronic Acid (HA) is a lubricant that enables normal sliding between the deep fascia and the epimysium.21 Ex- cessive accumulation of HA in the Extracellular Matrix (ECM) of muscle can dramatically increase its viscosity and alter its lubricating properties. Viscosity of the ECM has not been traditionally considered to contribute to passive resistance in muscles. Muscle overactivity due to spasticity has been associated with hyperviscous ECM. The resulting increase in passive resistance to movement and reduction in force transmission can lead to muscle stiffness.22,23 It is not just the accumulation of hyaluronic acid, but also the polymerization of HA that increases the viscosity of the ECM. The polymerization of HA has been affiliated with cites of CC’s as well as increase in HA itself.24 The role polymerization of HA plays beyond just volume increases of HA is further elaborated by many other scientists and the thought is offered for consideration. In a controlled clinical study, 3D-T1P magnetic resonance imaging was used to compare HA quantity in muscles of five healthy participants to that of five post-stroke patients with stiffness. It was found that HA concentration in patients with post-stroke muscle stiffness is higher compared to controls.25,26 Other small clinical trials showed that after treating patients with post-stroke muscle stiffness with intramuscular hyaluroni- dase injection, there was a significant improvement in stiff- ness and an increase in passive and active movement.25-28 Increased viscosity of hyaluronic acid and acidification of extracellular matrix lead to dysfunction of fascia. When dysfunction occurs, FM can reduce viscosity in loose connective tissue, and this result can be reflected by ultra- sound.29 Stecco FM has been widely used in the treatment of musculoskeletal diseases in recent years, which can ef- fectively reduce pain and improve disability.30 Although the exact mechanism has not been explained, we argue that the mechanism of Fascial Manipulation may relieve spasticity by modulation of the following factors: i) it stimulates the central nervous system and autonomic nervous system at the same time; the regulation of the cen- tral nervous system reduces the overall muscle tension, while the autonomic nervous system reduces the tension by dilating blood vessels and reducing tissue viscosity to - 17 - Table 4. Comparison of lower limb FMA before and after treatment between 2 groups (X±S). Group Number Pre-treatment Post-treatment t P Control group 20 12.85±5.39 18.95±6.27a -6.118 0.000 FM Group 20 14.45±4.34 23.35±3.45ab -10.682 0.000 t -1.033 -2.746 P 0.308 0.010 Table 5. Comparison of MAS before and after treatment between 2 groups (X±S). Group NumberPre-treatment Post-treatment t P Control group 20 2.80±0.70 2.35±0.75a 2.932 0.009 FM Group 20 2.85±0.67 1.80±0.70ab 5.294 0.000 t -0.231 2.971 P 0.818 0.005 Non -co mmerc ial us e o nly Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 relieve spasms; ii) it can effectively reduce the viscoelas- ticity of extracellular matrix, and tissue stiffness and in- crease the sliding between collagen fiber layers of deep fascia caused by the accumulation of hyaluronic acid, re- lieving spasm; iii) fascia can actively contract has abun- dant innervation, and is rich in proprioceptors such as Ruffini and Pacini corpuscles, which can sense changes in tension.31 Restoring the physiologic state of the fascia can improve nerve response and stimulate proprioception at the same time. In a study on ankle spasms in stroke patients with hemi- plegia, Mirbagheri et al.32 observed changes in neuromus- cular characteristics throughout the entire range of ankle motion. They found that nerve reflexes combined with pe- ripheral factors such as muscle and connective tissue change to limit ankle movement. Among them, the move- ment limitation caused by nerve reflexes was most ob- vious in the neutral ankle position, while the changes of peripheral factors such as muscle characteristics in- fluenced the angle of ankle dorsiflexion to a greater extent. In the present study, after a course of treatment, the PROM of the ankle joint was significantly enlarged in the obser- vation group, which we can assume is the result of FM. Therefore, stroke patients with hemiplegia, due to tibial anterior muscle weakness and triceps spasm of the calf, are mostly manifested as foot drop, foot varus, limited dorsiflexion of the ankle, and even the development of Achilles tendon contracture retraction. The effect of Fas- cial Manipulation is to reduce the degree of leg spasticity by affecting the peripheral mechanism. The reduction of spasticity can improve the strength of the tibial anterior muscle on the hemiplegic side by influencing the recipro- cal inhibition and combining it with routine rehabilitation training,33 thus greatly increasing the range of motion of the ankle joint and improving the lower limb function (ex- pressed as FMA score) on the hemiplegic side, which is consistent with the results of this study. In the treatment of patients with hand spasms after stroke, Zhang Zengqiao et al.34 found that acupuncture of Feng’s fascia point could effectively relieve spasms. Liu Baoguo et al.35 applied the theory of myofascial injury to stroke patients to relieve spasms through acupuncture, massage, and other ways. The efficacy of Chinese medicine acu- puncture fascia points to relieve spasmodic has been proven. Compared with acupuncture on the fascia point, the Stecco FM adopted in this study has the advantages of being non-invasive, having less pain, having an imme- diate effect, and having higher tolerance. However, there are still some limitations in this study. First of all, the sam- ple size included in this study is insufficient to completely exclude the influence of chance. Second, patients in the observation group were not followed up in this study to evaluate the long-term effect of FM. Third, FM should be investigated compared to actual therapy options such as shockwave therapy or botulinum toxin injection therapy. Finally, the mechanism of FM to relieve spasticity is still unclear and needs to be confirmed by a large number of studies. Therefore, the specific mechanism of FM to im- prove spasticity, as well as the medium- and long-term ef- ficacy needs further study. Conclusions Fascial Manipulation can effectively relieve spasticity of the lower limb and ankle clonus in stroke patients, and improve the passive range of motion of the ankle joint, and the motor function of the affected lower limb in the short term. It acts on the peripheral component of spasticity partially restoring physiological viscoelastic properties of the tissues and tissue gliding. As a new anti-spasmodic method, Fascial Manipu- lation has the advantages of being non-invasive, repeatable, and highly effective. It enhances the effect of conventional physiotherapy and can be proposed as an alternative or com- plementary to other therapies such as botulinum toxin. List of acronyms CC: Centers of Coordination. CSS: comprehensive spasticity scale. ECM: Extracellular Matrix. FM: Fascial Manipulation. FMA: Fugl-Meyer motor function score. HA: Hyaluronic Acid. MAS: Modified Ashworth Scale. PROM: passive range of motion. Contributions Conceptualization, CS and JW; methodology, WL; soft- ware, XL; validation, WL, XL, and YW; data curation, XL; writing—original draft preparation, WL; writing—review and editing, FG, CS; supervision, JW; project administra- tion, CS. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Institutional review board statement The study was conducted in accordance with the Declara- tion of Helsinki, and approved by the Ethics Committee of the First Hospital of Shanxi Medical University (2020 K- K088). Informed consent statement Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patients to publish this paper. Availability of data and materials The article does not publicly share research data. Acknowledgments The article does not accept any support given which is not covered by the author’s contribution or funding sections. - 18 - Non -co mmerc ial us e o nly Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 Conflicts of interest The authors declare no conflict of interest. Corresponding author Federico Giordani, Villa Rosa Neurological Rehabilitation Hospital, APSS Trento, Trento, Italy. ORCID ID: 0000-0001-7598-8189 E-mail: federico.giordi@gmail.com Wenyan Li, ORCID ID: 0009-0006-2402-9037 E-mail: wen198102@163.com Xin Liu, ORCID ID: 0009-0001-9764-7278 E-mail: robbie234@163.com Yinghua Wen, ORCID ID: 0009-0000-0423-3758 E-mail: 164932433@qq.com Junying Wu, ORCID ID: 009-0004-9841-6537 E-mail: wujunying777@126.com Carla Stecco ORCID ID: 0000-0002-8767-4555 E-mail: carla.stecco@unipd.it References 1. Lance JW. The control of muscle tone, reflexes, and movement: Robert Wartenbeg Lecture. Neurology 1980;30:1303-13. 2. Zeng H, Chen J, Guo Y, Tan S. Prevalence and risk fac- tors for spasticity after stroke: a systematic review and meta-analysis. Front Neurol 2021;11:616097. 3. Luo WY, Tang YM. Expert consensus on fall risk as- sessment and comprehensive intervention after stroke. J Clin Intern Med 2022;39:63-8. 4. Bethoux F. Spasticity management after stroke. Phys Med Rehabil Clin 2015;26:625-39. 5. Trompetto C, Marinelli L, Mori L, et al. Pathophysi- ology of spasticity: implications for neurorehabilitation. Biomed Res Int 2014;2014:354906. 6. Azzollini V, Dalise S, Chisari C. How does stroke affect skeletal muscle? State of the art and rehabilitation per- spective. Front Neurol 2021;12:797559. 7. Chinese Medical Association. Diagnostic points of various cerebrovascular diseases. Chin J Neurol 1996;6:60-1. 8. Stecco C, Day JA. The fascial manipulation technique and its biomechanical model: a guide to the human fas- cial system. Int J Ther Massage Bodywork 2010;3:38. 9. Yan TB. Study on the reliability of comprehensive spasm scale. Chin J Rehabil Med 2002;5:263-5. 10. Yan GB. Range of motion, ROM. Chin J Joint Surg Electron Ed 2014;8:409. 11. Lu ZY. Application of Fugl-Meyer scale in stroke re- habilitation assessment. J Clin Med 2016;3:2032-4. 12. Blackburn M, Van Vliet P, Mockett SP. Reliability of measurements obtained with the modified Ashworth scale in the lower extremities of people with stroke. Phys Ther 2002;82:25-34. 13. Katz RT, Rymer WZ. Spastic hypertonia: mechanisms and measurement. Arch Phys Med Rehabil 1989;70: 144-55. 14. Li S, Francisco GE. New insights into the pathophysi- ology of post-stroke spasticity. Front Hum Neurosci 2015;9:192. 15. Mirbagheri MM, Tsao C, Settle K, et al. Time course of changes in neuromuscular properties following stroke. In: 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. Piscata- way: IEEE; 2008, pp 5097-5100. 16. Arasaki K, Igarashi O, Ichikawa Y, et al. Reduction in the motor unit number estimate (MUNE) after cerebral infarction. J Neurol Sci 2006;250:27-32. 17. Kesikburun S, Yaşar E, Adıgüzel E, et al. Assessment of spasticity with sonoelastography following stroke: a feasibility study. PM R 2015;7:1254-60. 18. Jalal NIM, Gracies JM, Zidi M. Mechanical and micro- structural changes of skeletal muscle following immo- bilization and/or stroke. Biomech Model Mechanobiol 2020;19:61-80. 19. Stecco A, Stecco C, Raghavan P. Peripheral mech- anisms contributing to spasticity and implications for treatment. Curr Phys Med Rehabil Rep 2014; 2:121-7. 20. Adstrum S, Hedley G, Schleip R, Stecco C, Yucesoy CA. Defining the fascial system. J Bodyw Mov Ther 2017;21:173-7. 21. McCombe D, Brown T, Slavin J, Morrison W. The his- tochemical structure of the deep fascia and its structural response to surgery. J Hand Surg 2001;26:89-97. 22. Rasool G, Wang AB, Rymer WZ, Lee SS. Shear waves reveal viscoelastic changes in skeletal muscles after hemispheric stroke. IEEE Trans Neural Syst Rehabil Eng 2018;26:2006-14. 23. Wang AB, Perreault EJ, Royston TJ, Lee SS. Changes in shear wave propagation within skeletal muscle during active and passive force generation. J Biomech 2019;94:115-22. 24. Pavan PG, Stecco A, Stern R, Stecco C. Painful con- nections: densification versus fibrosis of fascia. Curr Pain Headache Rep 2014;18:441. 25. Menon RG, Raghavan P, Regatte RR. Quantifying mus- cle glycosaminoglycan levels in patients with post- stroke muscle stiffness using T1ρ MRI. Sci Rep 2019;9:14513. 26. Menon RG, Oswald SF, Raghavan P, Regatte RR, Stecco A. T1ρ-mapping for musculoskeletal pain dia- gnosis: Case series of variation of water bound glyco- saminoglycans quantification before and after fascial manipulation® in subjects with elbow pain. Int J Envi- ron Res Public Health 2020;17:708. 27. Raghavan P, Lu Y, Mirchandani M, Stecco A. Human recombinant hyaluronidase injections for upper limb - 19 - Non -co mmerc ial us e o nly mailto:federico.giordi@gmail.com mailto:robbie234@163.com Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation | Maccarone & Masiero Eur J Transl Myol 12172, 2024 doi: 10.4081/ejtm.2024.12172 muscle stiffness in individuals with cerebral injury: a case series. EBioMedicine 2016;9:306-13. 28. Raghavan P. Emerging therapies for spastic movement disorders. Phys Med Rehabil Clin 2018;29:633-44. 29. Hughes E, Koenig JM, Lee RS, McDermott K, Freil- icher T, Pitcher MH. Pilot study assessing the effect of Fascial Manipulation on fascial densifications and as- sociated pain. Eur J Transl Myol 2022;32:10369. 30. Arumugam K, Harikesavan K. Effectiveness of fascial manipulation on pain and disability in musculoskeletal conditions. A systematic review. J Bodyw Mov Ther 2021;25:230-9. 31. Morley J, Fan C, McDermott K, Fede C, Hughes E, Stecco C. The crural interosseous membrane re-visited: a histological and microscopic study. Eur J Transl Myol 2019;29:8340. 32. Mirbagheri MM, Alibiglou L, Thajchayapong M, Rymer WZ. Muscle and reflex changes with varying joint angle in hemiparetic stroke. J Neuroeng Rehabil 2008;5:6. 33. Hara T, Abo M, Hara H, Sasaki N, Yamada N, Niimi M, Shimamoto Y. The effect of repeated botulinum toxin A therapy combined with intensive rehabilitation on lower limb spasticity in post-stroke patients. Toxins 2018; 10:349. 34. Zhang ZQ, Li KP, Zhu Y, Zhou P, Hu CD, Hu XS, Feng W. Preliminary observation on clinical efficacy of Feng’s fascia point on relieving hand spasm after stroke. Shanghai J Tradit Chin Med 2018;52:66-8. 35. Liu BG, Wu J, Li ZY, You QZ, Le S. Current situation and treatment of myofascial injury in stroke patients. Med Forum 2021;25:2375-7. Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their af- filiated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Submitted: 11 December 2023. Accepted: 29 May 2024. Early access: 3 July 2024. - 20 - Non -co mmerc ial us e o nly