Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and patients are affected for the rest of their lives.Currently,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal spasticity.However,none of these methods can provide full symptom relief.This has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and safety.AIM To analyze the efficacy and safety of MSCT in CP patients.METHODS Our sample consists of four CP patients who cannot stand or walk without external support.All of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)instruments.We utilized the Modified Ashworth Scale(MAS)to measure spasticity.RESULTS We found significant improvements in MAS scores after the intervention on both sides.Two months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046.However,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity,and it partially improves motor functions.

Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhib- its satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in im- proving the spasticity post-stroke, more prospective cohort studies involving large sample sizes are needed.

Different frequencies of repetitive transcranial magnetic stimulation combined with local injection of botulinum toxin type A for post-stroke lower limb spasticity:study protocol for a prospective,single-center,non-randomized,controlled clinical trial

No definite consensus has currently been reached regarding the safety and efficacy of low-or high-frequency repetitive transcranial magnetic stimulation in the treatment of post-stroke muscle spasticity.The latest research indicates that when combined with local injections of botulinum toxin type A,it is more effective on post-stroke muscle spasticity than local injections of botulinum toxin type A alone.We designed a prospective,single-center,non-randomized,controlled clinical trial to investigate the safety and effica cy of different frequencies of repetitive transcranial magnetic stimulation combined with local injections of botulinum toxin type A in treating post-stroke lower limb muscle spasticity to determine an optimal therapeutic regimen.This trial will enroll 150 patients with post-stroke muscle spasticity admitted to the Department of Rehabilitation Medicine at the First Affiliated Hos pital of China Medical Unive rsity.All enrolled patients will undergo ro utine rehabilitation training and will be divided into five groups in-30 per group) according to the particular area of cerebral infa rction and treatment methods.G roup A:Patients with massive cerebral infarction will be given local injections of botulinum toxin type A and low-frequency(1 Hz)repetitive transcranial magnetic stimulation on the contralate ral side;G roup B:Patients with non-massive cerebral infarction will be given local injections of botulinum toxin type A and high-frequency(10-20 Hz) re petitive transcranial magnetic stimulation on the affected side;G roup C:Patients with massive/non-massive cerebral infarction will be given local injections of botulinum toxin type A;G roup D:Patients with massive cerebral infarction will be given low-frequency(1 Hz) repetitive transcranial magnetic stimulation on the contralate ral side;and G roup E:Patients with non-massive cerebral infa rction will be given high-frequency(10-20 Hz) repetitive transcranial magnetic stimulation on the affected side.The primary outcome measure of this trial is a modified Ashwo rth scale score from 1 day before treatment to 12 months after treatment.Secondary outcome measures include Fugl-M eyer Assessment of Lower Extremity,Visual Analogue Scale,modified Barthel index,and Berg Balance Scale scores for the same time as specified for primary outcome measures.The safety indicator is the incidence of adverse events at 3-12 months after treatment.We hope to draw a definite conclusion on whether there are diffe rences in the safety and efficacy of low-or high-frequency repetitive transcranial magnetic stimulation combined with botulinum toxin type A injections in the treatment of patients with post-stroke lower limb spasticity under strict grouping and standardized operation,thereby screening out the optimal therapeutic regimen.The study protocol was approved by the Medical Ethics Committee of the First Affiliated Hospital of China Medical University(approval No.[2021] 2021-333-3) on August 19,2021.The trial was registe red with the Chinese Clinical Trial Registry(Registration No.ChiCTR2100052180) on October 21,2021.The protocol version is 1.1.

Effect of An-pressing manipulation on post-stroke muscle spasticity in rats and its mechanism study

Objective:To explore the mechanism of An-pressing manipulation in improving post-stroke muscle spasticity,by observing the changes of γ-aminobutyric acid(GABA)and glycine(GIy)in plasma and gray matter of L1-L3 spinal cord anterior horn in post-stroke rats with muscle spasticity after An-pressing manipulation intervention.Methods:Ten of 80 adult male Sprague-Dawley(SD)rats were randomly selected as the blank group,and the remaining 70 were used for modeling.The middle cerebral artery occlusion(MCAO)rat model was established by insertion suture occlusion method in the left external carotid artery.Thirty rats with a Longa neurological score of 2-3 points and a modified Ashworth spasticity scale score of 1,1+,or 2 were included in the experiment.Using the random number table method,the 30 successfully modeled rats were randomly divided into a model group,an An-pressing tendon group and an An-pressing muscle belly group.Two days after modeling,rats in the An-pressing tendon group and An-pressing muscle belly group received An-pressing manipulation on the tendon and belly of quadriceps femoris muscle respectively,with the pressure of(350±50)g and the frequency of 5 s/time,15 min per session,once a day for 5 continuous days.After the 5th treatment,the tension of the rat quadriceps femoris muscle was evaluated using the modified Ashworth spasticity scale.The Gly levels in rat plasma and L1-L3 segments of spinal cord were determined by enzyme-linked immunosorbent assay(ELISA).The GABA levels in rat plasma and L1-L3 segments of spinal cord were measured by high performance liquid chromatography(HPLC).Results:The decrease in rat muscle tension scored by the modified Ashworth spasticity scale in the An-pressing tendon group was more significant than that in the An-pressing muscle belly group(P<0.01);the increases in Gly and GABA levels in the rat plasma and L1-L3Segments of spinal cord were more significant in the An-pressing tendon group than those in the An-pressing muscle belly group(all P<0.01).

Effect of row needling in muscle regions combined with seven-star needle tapping on cognitive function and quality of life in patients with post-stroke upper limb spasticity

Objective：To observe the effect of row needling in muscle regions combined with seven-star needle tapping on cognitive function and quality of life （QOL） in patients with post-stroke upper limb spasticity. Methods： A total of 448 eligible cases were randomly allocated into a treatment group and a control group, 244 in each group. Based on standard conventional treatment, cases in the treatment group received row needling in muscle regions combined with seven-star needle tapping, whereas cases in the control group took oral Western medication. After 3 weeks of treatment, the cognitive functions were assessed using comprehensive functional assessment （CFA） and mini-mental state examination （MMSE）. The O,OL was evaluated using the Chinese-version 36-item short-form health survey （SF-36）. Results： After treatment, the CFA and MMSE scores were significantly improved in both groups （P〈0.05）; and there were between-group statistical differences （P〈0.05）, showing a better effect in the treatment group than that in the control group. In addition, there were between-group statistical significances in scores of QOL （P〈0.05, P〈0.01）. Conclusion： Row needling in muscle regions combined with seven-star needle tapping can significantly improve the cognitive function and O, OL of patients with post-stroke upper limb spasticity.

Effect of catgut implantation at acupoints on GABA_B and mGluR1 expressions in brain stem of rats with spasticity after stroke

OBJECTIVE: To investigate the effect of catgut implantation at acupoints on the expressions of γ-amino butyric acid B receptor(GABAB ) and metabotropic glutamate receptor 1(mGluR1) in the brain stem of rats with spasticity after stroke.METHODS: In total, 60 male Sprague-Dawley rats were randomly divided into three groups: a sham group(n=10), a model group(n=25) and a treatment group(n=25). The rats in both the model group and the treatment group were subjected to middle cerebral artery occlusion to establish a model of focal cerebral ischemia. Rats with limb-spasm met the inclusion criteria. Only the left carotid artery was isolated in sham group rats. Three days after modeling, the treatment group was subjected to catgut implantation at Dazhui(GV 14), Guanyuan(CV 4), and Zhongwan(CV 12). Neurological deficit symptoms were assessed with the Zea-Longa neurological deficit score. The Modified Ashworth Scale(MAS), and isolated muscle tone were used to evaluate spasticity before and after treatment. Immunohistochemistry was applied to determine the expression of GABAB and mGluR1 in the rat brain stem after treatment.RESULTS: After treatment, neural impairment symptoms had significantly improved in the treatment group when compared to the model group(P<0.05). Both MAS and isolated muscle tone in the treatment group were significantly decreased when compared with the model group(P<0.05),and were also lower than before treatment. GABAB expression was significantly higher and mGluR1 was lower in the treatment group when compared with the model group(P<0.01 and P<0.05, respectively).CONCLUSION: Catgut implantation at Dazhui(GV 14), Guanyuan(CV 4), and Zhongwan(CV 12), can relieve limb spasticity by increasing the expression of GABAB and reducing the expression of mGluR1 in the brain stem of rats after stroke.

Clinical observation on acupoint pressure plus long-snake moxibustion for upper-limb spastic hemiplegia after cerebral infarction

Objective To observe the clinical efficacy of acupoint pressure plus long-snake moxibustion for upper-limb spastic hemiplegia after cerebral infarction.Methods A total of 100 patients were randomized into a control group and an observation group,with 50 cases in each group.Both groups were treated with the same conventional internal medicine and rehabilitation training.The control group was treated with additional acupoint pressure therapy,and the observation group was treated with long-snake moxibustion on the basis of the treatment given to the control group.The Ashworth grade,Fugl-Meyer assessment upper limb scale(FMA-UL)and Barthel index(BI)were evaluated,and the root mean square(RMS)values of biceps brachii and flexor carpi radialis on the affected side were measured before and after treatment.The efficacy was evaluated after treatment.Results After treatment,the total effective rate of the observation group was significantly higher than that of the control group(P<0.05).After treatment,the Ashworth grade of the observation group was superior to that of the control group(P<0.05).The scores of FMA-UL and BI in both groups increased compared with those before treatment(all P<0.05),and the scores of FMA-UL and BI in the observation group were higher than those in the control group(both P<0.05).The RMS values of biceps brachii and flexor carpi radialis in both groups decreased compared with those before treatment(all P<0.05),and the RMS values of biceps brachii and flexor carpi radialis in the observation group were lower than those in the control group(both P<0.05).Conclusion Based on conventional internal medicine and rehabilitation training,acupoint pressure plus long-snake moxibustion has great therapeutic efficacy for upper-limb spastic hemiplegia after cerebral infarction.It can improve the degree of spasticity of the affected upper limb,reduce the muscle tone of biceps brachii and flexor carpi radialis on the affected side,and enhance the mobility of the affected limb and the activities of daily living.

The current state of knowledge on the clinical and methodological aspects of extracorporeal shock waves therapy in the management of post-stroke spasticity-overview of 20 years of experiences

Background and objectives In many patients after stroke, spasticity develops over time, resulting in a decrease in the patient′s independence, pain, worsening mood, and, consequently, lower quality of life. In the last ten years, a rich arsenal of physical agents to reduce muscle tone such as extracorporeal shock therapy (ESWT) wave has come through. The aim of this narrative review article is to present the current state of knowledge on the use of ESWT as a supplement to the comprehensive rehabilitation of people after stroke suffering from spasticity.Methods The PubMed and PEDro databases were searched for papers published in English from January 2000 to December 2020, 22 of which met inclusion criteria for clinical studies related to post-stroke spasticity management with ESWT.Results A total of 22 studies including 468 post-stroke patients-11 reports with the upper limb (267 patients) and 10 reports within the lower limb (201 patients), as well as one report including both upper and lower limb. We focused our attention on clinical and methodological aspects. Therefore, we performed the assessment of enrolled studies in terms of methodological quality using the PEDro and level of evidence using the National Institute for Health and Clinical Excellence (NICE) guidelines. Furthermore, we indicated implications for clinical practice in using ESWT for post-stroke spasticity management. Moreover, we discussed a suggestion for future research directions.Conclusions In conclusion, an ESWT effectively reduces muscle tone in people with spastic limb after stroke. Further, ESWT is safe and free of undesirable side effects.The mechanism of action of ESWT on muscles affected by spasticity is still unknown.To date, no standard parameters of ESWT in post-stroke spasticity regarding intensity, frequency, location, and the number of sessions has been established. Further research, meeting the highest standards, is needed to establish uniform muscle stimulation parameters using ESWT.