Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

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.

Effect of VOJTA Therapy on Gross Motor Function in Children with Cerebral Palsy

Objective: To investigate the effect of VOJTA therapy on gross motor function in children with cerebral palsy. Methods: The 86 children with cerebral palsy were all from the First People’s Hospital of Jingzhou City from January 2023-December 2023, and were divided into the control group and the study group with 43 cases according to the principle of voluntariness. Results: In terms of total effective rate of treatment, the gross motor function scale-88 (GMFM-88) was used to evaluate the effective rate before and after treatment, and the effective rate of the study group was higher than that of the control group, and the difference was statistically significant, and the scores of gross motor items of GMFM-88 were better than those of the control group after treatment, and the difference was statistically significant (P 0.05). Conclusion: The application of VOJTA therapy in the treatment of children with cerebral palsy can not only promote the rehabilitation of gross motor function, but also help to improve the treatment effect, and the earlier the treatment, the better.

Mothers’challenges and experiences of children with cerebral palsy:a qualitative meta-synthesis

Objective:To examine what challenges and experiences a mother faces in caring for children with cerebral palsy(CP).As the main caregiver of children with CP,mothers are under multiple pressures.Even though mothers’challenges and experiences of children with CP will affect their quality of life and the rehabilitation of the children,little is known about their challenges and experiences during the whole care.Methods:A qualitative meta-synthesis was conducted to extract and analyze qualitative research from the PubMed,CINAHL,PsycINFO,Web of Science,Ovid and MEDLINE databases.Thirteen articles were selected and analyzed using thematic syntheses.Results:From 2522 screened abstracts,84 texts were reviewed,and 13 studies met the inclusion criteria.Mothers’challenges and experiences of children with CP include 4 themes,both positive and negative.Conclusions:The mothers of children with CP suffer from physical burden,as well as psychological pressure,in the care experience;social and healthcare support are their main challenges.Interventions to help them face the difficulties and adapt to the role of caregivers as soon as possible should target multiple aspects in order to maximize effectiveness,to promote the healthy growth of children with CP.

An overview of acupuncture for the treatment of limb spasticity in cerebral palsy-A mini review

Cerebral palsy is a common chronic disabling disease in children with special needs,and rehabilitation for cerebral palsy is characterized by a long period,multiple methods and limited efficacy.Due to the limited motor function of cerebral palsy patients,the quality of life of patients is reduced,and their ability to participate in society is reduced,so the improvement of patients’motor function has become an important goal of cerebral palsy rehabilitation.The motor function of cerebral palsy has become an important goal of cerebral palsy rehabilitation.Limb spasticity is one of the main clinical signs of cerebral palsy patients,and the more severe the limb spasticity is,the greater the impact on the patient's motor function,so improving limb spasticity in patients with cerebral palsy is particularly important.Acupuncture,as a Chinese medicine treatment method,has been widely used in the clinical treatment of cerebral palsy in China,and has shown certain efficacy.To promote the clinical application of acupuncture technique in cerebral palsy limb spasticity,this paper analyses and summarizes the relevant literature on acupuncture treatment of cerebral palsy limb spasticity summarizes the current status of the clinical application of acupuncture in cerebral palsy limb spasticity,and provides clinical references for the reasonable application of acupuncture in cerebral palsy limb spasticity.

Clinical Study on Improving Articulation Clarity in Spastic Cerebral Palsy with 120 Cases of Oral-Facial Acupressure Combined with Oral Placement Therapy

Objective:To observe the efficacy of oral-facial acupressure combined with oral placement therapy(OPT)in improving articulation clarity in 120 children with spastic cerebral palsy,and to explore effective therapeutic solutions for speech disorders associated with spastic cerebral palsy.Methods:A total of 120 children with spastic cerebral palsy and speech disorders,meeting the inclusion criteria,were randomly assigned into two groups:60 cases in the treatment group and 60 cases in the control group.The treatment group received orofacial acupressure combined with OPT,while the control group received only OPT.The Oral Motor Function Assessment Scale(OMFAS),developed by the China Rehabilitation Research Centre(CRRC),was used to evaluate the treatment outcomes before and after the intervention.Results:After the treatment,both the treatment and control groups showed improved mobility of the mandible,lips,and tongue.However,the treatment group exhibited significantly better improvement than the control group,with the difference between the two groups being statistically significant(P<0.05).Conclusion:Oral-facial acupressure combined with OPT can effectively improve articulation clarity in children with spastic cerebral palsy.This combined therapy is recommended for clinical promotion and application.

Effects of video game-based therapy in an adolescent with cerebral palsy: A case report

BACKGROUND Herein,we report the case of a 13-year-old boy with spastic quadriplegia cerebral palsy(CP)at Gross Motor Function Classification System(GMFCS)level II,en-gaging in a 6-wk video game-based therapy(VBT)program.This study aimed to offer essential insights regarding VBT’s impact on enhancing the physical function and improving the quality of life(QoL)of adolescents diagnosed with CP.This report provides a distinctive viewpoint that can inform and direct future clinical practices and research endeavors.CASE SUMMARY The boy presented with moderate mobility,balance,and overall well-being.He faced challenges with diminished lower limb strength,which affected his daily living and physical fitness capabilities.Our participant was diagnosed with spas-tic quadriplegic CP at GMFCS level II.He participated in a 6-wk program of VBT using a play station.This innovative approach incorporates warm-up exercises,interactive activities,and cool-down routines,targeting various movements,in-cluding single-leg stance,weight shifting,kicking,jumping,marching,and squatting.After VBT,the strength of the left hip extensor significantly increased from 199.3 N to 541.3 N.Distance covered as part of a 6-min walk test increased by 82 m.His Paediatric QoL Inventory score increased dramatically by 25.9%.CONCLUSION VBT is an innovative,individualized therapy that enhances physical function and QoL in CP,emphasizing its role in ambulatory patients.

Precise Rehabilitation Strategies for Functional Impairment in Children with Cerebral Palsy

This paper explores the effect of precise rehabilitation strategies under the international classification of functioning,disability and health for children and youth(ICF-CY)on the motor function of children with cerebral palsy.Under the framework of ICF-CY,the observation team is designed and evaluated from physical functions,activities and participation,environmental factors,and devel-ops individualized rehabilitation strategies that are tailored to individual character-istics.The control group was assessed by traditional methods and treatment plans and measures were formulated and guided.The course of treatment was 12 months.The scores of GMFM-88,Peabody Motor Development Scale-2con-cluding fine motor quotient(PDMS-FM),WeeFIM and the ability of daily living(ADL)scale(Barthel index,BI)score were compared before and after treatment.The research shows that precise rehabilitation strategy mode for children with cer-ebral palsy under the ICF-CY framework can effectively improve the motor func-tion and the ability of daily living(ADL)in children with cerebral palsy.Rehabilitation evaluation and treatment mode of children with cerebral palsy under ICF-CY framework can effectively improve the gross motor function of children with cerebral palsy.Individualized evaluation and analysis and guidance of comprehensive rehabilitation treatment have certain advantages.The overall treatment effect is better than that of traditional rehabilitation evaluation.

Systematic evaluation of the efficacy and safety of botulinum toxin type A in the treatment of spastic cerebral palsy

Background:Botulinum toxin type A(BTX-A)is a neuromuscular blocking agent.BTX-A inhibits acetylcholine release,causes neuromuscular transmission impairment,and decreases muscle spasms.Objective:To explore the efficacy and safety of BTX-A injection in the treatment of spastic cerebral palsy through systematic evaluation and to provide a reference for the clinical use of BTX-A.Methods:We used“Cerebral palsy”and“BTX-A”as the subject terms and used a combination of subject terms and free words for the search.We searched 7 databases,including CNKI,Wanfang,VIP,Sinomed,PubMed,Embase,and Web of science.Based on the inclusion and exclusion criteria,we screened the articles by reading their titles,abstracts,and full texts and finally included relevant literature for systematic evaluation.Result:A total of 93 papers were systematically evaluated,revealing that BTX-A injection treatment can effectively reduce muscle tone,increase joint mobility,improve gait and motor posture,and enhance gross motor movements in patients with spastic cerebral palsy.The benefits of BTX-A treatment can be sustained for 3–6 months,with motor ability improvement lasting up to 1 year.Combining BTX-A treatment with rehabilitation or external fixation therapy can enhance its efficacy.However,the effectiveness of BTX-A treatment is influenced by several factors,such as the dosage,number of injections,and patient age.Adverse reactions to BTX-A treatment are typically mild and can be relieved within 1–2 weeks.Conclusion:BTX-A injection is relatively safe but reversible.

Effect of Lumbar Spinal Point Injection on Sitting Function in Children with Cerebral Palsy

Objective: To observe the effect of lumbar spinal point injection on sitting function in children with cerebral palsy. Method: Sixty-two children with post-confirmed cerebral palsy were randomly divided into control group and treatment group, 31 each. The control group was given conventional rehabilitation treatment, and the treatment group was given lumbar chiropspinal acupoint injection on the basis of the treatment method of the control group. After 3 consecutive courses of treatment, the sitting score of the two groups before and after treatment (GMFM88) was used to evaluate the sitting score before and after treatment. Outcome: Before treatment, the two groups were evaluated and the differences were not statistically significant (p > 0.05), which was comparable. The two groups (GMFM88) after treatment had significantly increased the differential values, and the difference was statistically significant compared with the same group before treatment (p Conclusion: Conventional rehabilitation combined with lumbar spinal point injection can effectively improve the sitting motor function of children with cerebral palsy.

Research progress regarding the nutritional status and assessment methods of cerebral palsy patients

Cerebral palsy is a group of clinical disorders characterized by persistent central motor deficits and postural abnormalities due to non-progressive damage to the fetal or infant brain.Malnutrition is one of the most common clinical comorbidities in children with cerebral palsy and is the result of a combination of internal factors,such as the child’s structural and functional abnormalities,and external factors,such as the child’s feeding habits and family/social factors.The nutritional status of children with cerebral palsy is closely related to their development,quality of life,social participation,and life expectancy;thus,an objective and accurate understanding of the nutritional status of these children through rehabilitation assessment is essential for their growth and development.The current nutritional assessments include routine measurements of human nutritional parameters,scale-based assessments,and instrumental assessments.It is important to detect malnutrition in children with cerebral palsy at an early stage,reduce the prevalence of malnutrition,and improve the quality of survival.Therefore,this review aimed to analyze and summarize the nutritional status and assessment methods of children with cerebral palsy,to assess the nutritional status of children with cerebral palsy from multiple perspectives,indicators and directions,and to provide reference for the early detection of co-morbid malnutrition in children with cerebral palsy.

CLINICAL RESEARCH OF JIAJI(夹脊EX-B2) IN TREATMENT OF SPASTIC CEREBRAL PALSY WITH ACUPUNCTURE

Objective To observe the clinical therapeutic effects of Jiájǐ（夹脊EX-B2） on spastic cerebral palsy （SOP） with acupuncture.Methods 62 cases of SOP were randomized into two groups,named treat- ment group with acupuncture on Jiájǐ（夹脊EX-B2）,and control group with sham-acupuncture.The treatment was applied once a day,10 times made a course,totally 6 courses were required.Modified Ashworth scale and FIM grade were used to observe and assess the results of treatment.Results The total effective rate was 84.4 % in treatment group and was 63.3 % in control group,indicating significant difference （P〈0.01）. Conclusion Acupuncture on Jiájǐ（夹脊EX-B2） achieves good clinical therapeutic effects on SCP.

CURRENT SITUATION OF CHINESE REHABILITATION TREATMENT OF CEREBRAL PALSY

Analyze present situation of treatment of cerebral palsy at home and abroad, review in detail concrete methods and studies of mechanisms of acupuncture and moxibustion as main therapeutic way adopted at home, probe characteristics and models of Chinese rehabilitation treatment for cerebral palsy. Results indicate that acupuncture and moxibustion treatment of cerebral palsy has very great potential social and economic results. Therefore, it is appropriate to approach establishment of a comprehensive rehabilitation system of cerebral palsy with Chinese characteristics, and with acupuncture and moxibustion used as main way.

A Randomised Controlled Study to Investigate Effects of Bobath Based Trunk Control Training on Motor Function of Children with Spastic Bilateral Cerebral Palsy

Purpose: The aim of this study was to investigate the effects of trunk control on motor function, which plays an important role in the daily activities of children with Cerebral Palsy (CP) and is often observed as a deficiency in children with CP. Material and Methods: Forty children with spastic bilateral CP, ages between 3 to 10 years and with Gross Motor Function Classification System (GMFCS) level I, II, and III were included in this study. Children were divided into two groups using randomization and in training group;Bobath Therapy for trunk control in addition to classical physiotherapy programs was performed for 45 minutes, for two days a week, for 6 weeks. In control group, existing physiotherapy program, 45 minutes for two days a week, continued. Any addition was not made into the existing program of the control group. Modified Ashworth Scale (MAS), Pediatric Berg Balance Scale (PBBS), Trunk Control Measurement Scale (TCMS), 1 Minute Walking Test (1MWT), Timed Up and Go Test (TUG) were applied to both groups before and after 6 weeks. Moreover, trunk muscle strength of children was evaluated. Results: After therapy, differences were found in results of MAS and PBBS, and trunk extensor strength between the training group and the control group in favor of the training group (p Conclusion: This study shows that adding exercises which aim trunk to conventional physiotherapy and exercise programs of children with CP, affects motor function positively.

Research progress of Chinese and Western medicine on spastic cerebral palsy in children in recent ten years

In recent ten years,with more and more children with spastic cerebral palsy appearing around us,relevant clinical research has also become a research hotspot.However,at present,there is no radical plan for the treatment of children with spastic cerebral palsy in the world.This study summarizes the latest progress of traditional Chinese and Western medicine in the treatment of children with spastic cerebral palsy in recent years,hoping that the whole work can serve as a clinical and theoretical basis and provide certain reference significance.

Acupuncture for cerebral palsy: a meta-analysis of randomized controlled trials

OBJECTIVE： To evaluate the efficacy and safety of acupuncture therapy for children with cerebral palsy. DATA SOURCES： We conducted electronic searches of PUBMED（1950/2017）, EMBASE（1974/2017）, Science Direct（1986/2017）, Academic Source Premier（1887/2017）, the Cochrane Library（Issue 4, April 2017）, Science Citation Index Expanded（1900/2017）, China National Knowledge Infrastructure（1915/2017）, China Biological Medicine（1990/2017-04）, Wan Fang（1980/2017）, VIP（1989/2017）, and Chinese Science Citation Database（1989/2017）. DATA SELECTION： We included randomized controlled trials that aimed to compare the effect of acupuncture plus rehabilitation training versus rehabilitation training alone. Data about functional motor abilities, daily activity/social participation, effective rate, intellectual development, and adverse effects were included. We used Revman 5.2 software for statistical analysis. OUTCOME MEASURES： The primary outcomes included functional motor abilities, daily activity, and effective rate. The secondary outcomes included intellectual development and adverse effects.RESULTS： Twenty-one studies with a total of 1718 participants met the inclusion criteria. The effect size of gross motor function（SMD = 0.64, 95% CI： 0.52 to 0.76, P 〈 0.00001; I^2 = 0%, P = 0.69; in 13 studies with 1144 patients） and the total effective rate（RR = 1.28, 95% CI： 1.20 to 1.37, P 〈 0.00001; I^2 = 18%, P = 0.27; in 12 studies with 1106 patients） suggested that acupuncture plus rehabilitation produced a significant improvement in gross motor function and a high total effective rate. The pooled fine motor function（SMD = 3.48, 95% CI： 2.62 to 4.34, P 〈 0.00001; I^2 = 64%, P = 0.10; in 2 studies with 193 patients）, modified Ashworth scale scores（SMD = –0.31, 95% CI： –0.52 to –0.11, P = 0.003; I^2 = 74%, P = 0.004; in 5 studies with 363 patients） and activities of daily living（SMD = 1.45, 95% CI： 1.20 to 1.71, P 〈 0.00001; I^2 = 78%, P = 0.004; in 4 studies with 313 patients） also indicated improvements in children with cerebral palsy. Publication bias was not observed. Only mild adverse events related to acupuncture were reported. CONCLUSION： Acupuncture plus rehabilitation training improved gross motor function, reduced muscle spasms, and enhanced daily life activities in children with cerebral palsy. However, this conclusion should be interpreted with caution due to the small number of randomized controlled trials available and the small sample sizes. More high-quality and large-scale studies are needed.

Motor function outcomes of pediatric patients with hemiplegic cerebral palsy after rehabilitation treatment:a diffusion tensor imaging study

Previous diffusion tensor imaging （DTI） studies regarding pediatric patients with motor dys-function have conifrmed the correlation between DTI parameters of the injured corticospinal tract and the severity of motor dysfunction. There is also evidence that DTI parameters can help predict the prognosis of motor function of patients with cerebral palsy. But few studies are re-ported on the DTI parameters that can relfect the motor function outcomes of pediatric patients with hemiplegic cerebral palsy after rehabilitation treatment. In the present study, 36 pediatric patients with hemiplegic cerebral palsy were included. Before and after rehabilitation treatment, DTI was used to measure the ifber number （FN）, fractional anisotropy （FA） and apparent dif-fusion coefifcient （ADC） of bilateral corticospinal tracts. Functional Level of Hemiplegia scale （FxL） was used to assess the therapeutic effect of rehabilitative therapy on clinical hemiplegia. Correlation analysis was performed to assess the statistical interrelationship between the change amount of DTI parameters and FxL. DTI ifndings obtained at the initial and follow-up evalua-tions demonstrated that more affected corticospinal tract yielded signiifcantly decreased FN and FA values and signiifcantly increased ADC value compared to the less affected corticospinal tract. Correlation analysis results showed that the change amount of FxL was positively correlated to FN and FA values, and the correlation to FN was stronger than the correlation to FA. The results suggest that FN and FA values can be used to evaluate the motor function outcomes of pediatric patients with hemiplegic cerebral palsy after rehabilitation treatment and FN is of more signiif-cance for evaluation.

Differences in standing balance between patients with diplegic and hemiplegic cerebral palsy

Maintaining standing postural balance is important for walking and handling abilities in patients with cerebral palsy. This study included 23 patients with cerebral palsy （seven with spastic diplegia and 16 with spastic hemiplegia）, aged from 7 to 16 years of age. Standing posture balance measurements were performed using an AMTI model OR6-7 force platform with the eyes open and closed. Patients with diplegic cerebral palsy exhibited greater center of pressure displacement areas with the eyes open and greater center of pressure sway in the medial-lateral direction with the eyes open and closed compared with hemiplegic patients, Thus, diplegic patients exhibited weaker postural balance control ability and less standing stability compared with hemiplegic cerebral palsy patients.

Establishing a rat model of spastic cerebral palsy by targeted ethanol injection

Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxic instrument under intraperitoneal anesthesia. Based on the rat brain stereotaxic map, a 1-mm hole was made 10 mm posterior to bregma and 0.8 mm left of sagittal suture. A microsyringe was inserted perpendicularly to the surface of the brain to a depth of 9.7 mm, and 15 wL of ethanol was slowly injected to establish a rat model of spastic cerebral palsy. After modeling, the rats appeared to have necrotic voids in the pyramidal tract and exhibited typical signs and symptoms of flexion spasms that lasted for a long period of time. These findings indicate that this is an effective and easy method of establishing a rat model of spastic cerebral palsy with good reproducibility. Ethanol as a chemical ablation agent specifically and thoroughly damages the py- ramidal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease.

Progress in clinical trials of stem cell therapy for cerebral palsy

Cerebral palsy is the most common disease in children associated with lifelong disability in many countries.Clinical research has demonstrated that traditional physiotherapy and rehabilitation therapies cannot alone cure cerebral palsy.Stem cell transplantation is an emerging therapy that has been applied in clinical trials for a variety of neurological diseases because of the regenerative and unlimited proliferative capacity of stem cells.In this review, we summarize the design schemes and results of these clinical trials.Our findings reveal great differences in population characteristics, stem cell types and doses, administration methods, and evaluation methods among the included clinical trials.Furthermore, we also assess the safety and efficacy of these clinical trials.We anticipate that our findings will advance the rational development of clinical trials of stem cell therapy for cerebral palsy and contribute to the clinical application of stem cells.