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.

Metaphysical Energy Therapy in the Treatment of Cranial Nerve Palsies with Special Reference to Bell’s Palsy

Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (also named mononeuropathy). Com- monly 2 cranial nerves Viz., cranial nerve VII and cranial nerve VI are involved in facial nerve palsies. The former one is called Bell’s palsy and is acute Lower Motor Neuron facial nerve paralysis (>80%) causing an inability to control facial muscles on the affected side. The later one is sixth nerve palsy, (the abducens nerve), which is responsible for triggering contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye resulting in double vision on the affected side. In recent times, we have found to our amazement, rapid restoration of normalcy within a few hours to a few days, of Cranial Nerve palsies in diabetic subjects at our centre. We are presenting a group of cases having Type2DM over different time periods from 6 to 20 years and those who suddenly suffered facial nerve palsy and they came to VHSDRC for treatment. They were started on the new modality called the Dynamic Acupuncture Mediated Meta-physical Energy Therapy (DAMM Therapy), to recover from the facial palsy. The DAMM therapy is a unique novel way of infusing and transferring healing energy from the therapist to the patient. Within 2 - 7 sittings of DAMM therapy patients showed 75% - 100% improvement in their clinical condition.

Role of targeted neuromodulation in the treatment of congenital unilateral lower lip palsy:A clinical case report

Congenital unilateral lower lip palsy(CULLP),or congenital hypoplasia of the depressor anguli oris muscle,also known as asymmetric crying facies,is a rare condition that results in asymmetry of the lower lip during smiling,laughing,and crying.Although the etiology is unknown,weakness of the depressor labii inferioris(DLI)muscle is implicated as a contributing factor.Currently,no well-established treatment options are available.This case report describes an 18-year-old male patient diagnosed with CULLP.Physical examination revealed a symmetric face at rest,but asymmetry when smiling and opening the mouth.Following the administration of lidocaine into the affected DLI muscle,the patient’s smile and lower lip symmetry were immediately restored without any adverse effects.Subsequently,administration of botulinum toxin for neuromodulation of the DLI muscle led to a significant improvement in symmetry and oral function within 2 weeks,which was sustained at 1 month and 3 months post-treatment.No adverse effects were reported,and both patients and families expressed high satisfaction with the outcomes.This case highlights the potential use of neuromodulation as a minimally invasive and effective treatment for CULLP.

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.

The effect of breaking sitting time with physical activity breaks on cognitive performance in young people with cerebral palsy:an exposure response cross-over feasibility design

Objectives To assess the feasibility of methods and estimate the potential effect of interrupting sedentary behaviour,with intermittent or continuous physical activity breaks,on cognitive performance in young people with Cerebral Palsy.Methods A randomised three-arm exposure response cross-over design with process evaluation.Participants were recruited throughout the Thames Valley,UK between 01/11/2018 to 31/03/2020.The three 2 h activity exposure visits included:(i)sitting only(controls),(ii)sitting plus 20 min of moderate-to-vigorous activity burst,or(iii)4×5 min of moderate-to-vigorous activity bursts,during a 2.5 h sedentary session.Measures of feasibility were sought.Cognitive performance outcomes(using the Eriksen Flanker task and Forward and Backward Digit Span)were delivered before and after the 2 h testing period.Results 36 participants were randomised(age 13.2±2.7,Gross-Motor Functional Classification System 1–3).Study retention was 83%across all three interventions and overall missing data for measures was 4%.A small intervention effect was found in reaction time in the 4×5 min physical activity exposure session compared to the sedentary control condition(0.42;95%CI 0.40 to 0.79).There were two research-related minor adverse effects,an allergic reaction to the FreeStyle Libre and feeling faint and vomiting after consumption of glucose solution.Both events were resolved and participants continued with the study.Conclusions The study design and intervention implementing short bursts of physical activity was feasible and indicated a potential effect on reaction time as a measure of cognitive performance in young people with cerebral palsy.

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.

A Case Report on Treating Progressive Supranuclear Palsy with a Combination of Chinese and Western Medicine

A case of progressive supranuclear palsy in a 66-year-old woman is presented.The patient complained of“progressive stiffness of both lower limbs for five years,accompanied by choking and coughing for more than 1 year,”and was diagnosed with paralysis in traditional Chinese medicine(TCM),which was characterized by a deficiency of liver and kidney,and phlegm and blood stasis blocking the collaterals.Western medicine diagnosed it as progressive supranuclear palsy.The patient was diagnosed with“Parkinson’s disease”several times in the past and was given“polybasic hydrazide”and“amantadine hydrochloride tablets,”etc.The patient did not have significant symptomatic relief,so she sought further treatment with a combination of traditional Chinese and Western medicine.Based on the concept of deficiency and excess,this disease is categorized as a paralytic disease in Chinese medicine,and the onset of the disease is closely related to the deficiency of the body after a long period of illness,with wind,phlegm,blood stasis,and deficiency as the main pathogenetic mechanism.The treatment is based on the combination of disease and evidence,with traditional Chinese medicine and acupuncture as the main treatments,supplemented by intermediate-frequency pulsed electrical stimulation,transcranial repetitive magnetic stimulation,medicated canisters,wax therapy,traditional Chinese medicine guasha,and acupoint injections.Western medicine is based on symptomatic treatment,and the patient’s symptoms were relieved significantly after the combination of Chinese and Western medicine.

Etiological Analysis of 248 Cases of Oculomotor Nerve Palsy

Objective:To explore the main causes of oculomotor nerve palsy,providing a reference for clinical diagnosis and treatment.Methods:A total of 248 patients with oculomotor nerve palsy treated in the hospital from January 2016 to January 2018 were selected,and their causes and treatments were summarized.Results:This study found that the main causes of oculomotor nerve palsy were intracranial aneurysms,brain stem lesions,and brain inflammation.A few cases were due to viral infections and congenital oculomotor nerve palsy,while some patients had unknown causes.After treatment in our hospital,most patients experienced relief,although 12 patients died.Conclusion:The etiology of oculomotor nerve palsy is complex,and choosing appropriate drugs during treatment is challenging.Timely identification of the cause is an effective method for treatment.

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.

PROF.ZHANG ANLI'S EXPERIENCE OF TREATING STUBBORN CASES OF FACIAL PALSY

Based on her own experience of many years＇ clinical practice, Prof. Zhang Anli summarized and created the method in which the shallow insertion at the upper eyelid, acupuncture at the Back-shu points and balanced selection of points together with the modified Setting Mountain on Fire and application of Fire Needle were applied for the treatment of stubborn cases of facial palsy. The therapeutic effect is good.

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.

Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

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.

Effect of acupuncture on inflammatory cytokines expression of spastic cerebral palsy rats

Objective:To To investigate the effect of acupuncture on the tumor necrosis factor- α(TNF-α),interleukin-6(IL-6),C-reactive protein(CRP),nitric oxide synthase(NOS) content and muscular tension of spasticity cerebral palsy rat model.Methods:The rats with spastic cerebral palsy were randomly divided into the control group,model group and acupuncture group.After successful modeling,the muscular tension and the content of TNF- α,IL-6,CRP.NOS were measured.Results:The serum TNF- α,IL—6,CRP,NOS content were significantly decreased in the acupuncture group(P<0.05).The low and high shear viscosity of whole blood of the acupuncture group were significantly lower than the control group and the model group(P<0.05).The erythrocyte electrophoresis indexes in the acupuncture group were significantly lower than that in the model group and the control group(P<0.05).Acupuncture significantly reduced the muscular tension of spastic cerebral palsy rat and increased the active extent in the paralytie extremity(P<0.05),but it could not be restored to normal level.Compared with the control group,the difference had significant(P<0.05).Conclusions:Acupuncture treatment can inhibit the release of inflammatory cells after brain injury,then reduce immune injury,relieve muscle spasms and reduce muscular tension.

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.

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.

Infrared thermography and meridian-effect evidence and explanation in Bell's palsy patients treated by moxibustion at the Hegu (LI4) acupoint Overall regulation or a specific target?

Subjects with Bell＇s palsy and healthy individuals were treated with moxibustion thermal stimulation on the Hegu （LI4） acupoint; an infrared thermal imaging system was used to observe facial-temperature changes. Bell＇s palsy patients developed low or high temperatures at the affected side, with poor symmetry. Healthy people showed high temperatures on the forehead, medial angle of the eye, nasal ala and around the lips, but low temperatures on bilateral cheeks, thus forming a ＂T-type hot area＂ in the face, with good temperature symmetry. Moxibustion treatment for 11 minutes significantly improved high asymmetry in temperature in the faces of Bell＇s palsy patients. This evidence indicates that moxibustion treatment on Hegu enables increases in facial temperatures in healthy people and Bell＇s palsy patients, especially around the lips. Moxibustion stimulation at the Hegu not only improves the global circulation but also has specific effects on the lips in Bell＇s palsy patients, but the underlying mechanism needs further investigation.

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.