Effect of exercise rehabilitation and adapted physical activity on psychomotor skills, motor abilities and motor development in children and adolescents with spastic cerebral palsy: an evidence-based research using ICF / 中国康复理论与实践

ObjectiveTo systematically review the evidences of impact of exercise rehabilitation and adapted physical activity on psychomotor skills, motor abilities, and motor development in children with spastic cerebral palsy (CP). MethodsRelevant literature was retrieved from PubMed, Embase, Web of Science and CNKI, from January, 2010 to June, 2023. The contents were coded using International Classification of Diseases, Eleventh Revision, and International Classification of Functioning, Disability and Health; and evidences were analyzed with theoretical framework and code of ICD-11 and ICF. ResultsA total of nine articles were included, from Denmark, South Korea, Australia, Saudi Arabia, Ghana, India and Japan, published from 2015 to 2022. The intervention programs primarily involved exercise rehabilitation (including physical therapy) and adapted physical activity. Exercise rehabilitation included upper limb strength training, lower limb strength training, balance and coordination training, gait training, functional aerobic exercise, stretching and flexibility exercises, flexibility training, muscle relaxation techniques; ten to 50 minutes a time, two to six times a week,with the intensity of low to high, for six to 20 weeks. Adapted physical activities mainly involved adapted running training, virtual games; 60 minutes a time, two to four times a week, with the intensity of medium to high, for six to twelve weeks. Interventions primarily took place in medical and rehabilitation institutions, schools, and home-based communities, with professionals including occupational physical therapists, university researchers, community health personnel and teachers. The outcomes were mainly reflected in four aspects: psychomotor skills, motor abilities, motor development, and quality of life and well-being. In terms of psychomotor skills, adolescents with CP mastered running techniques and knowledge, and enhanced their response to balance threats. In terms of motor abilities, adolescents with CP showed an increase in muscle strength, enhanced muscle endurance, and an expansion of muscle tone; improvements in gait functionality, walking ability, and gait symmetry; increases in walking endurance; improvements in standing function; and improvements in dynamic balance; as well as enhanced control over balance posture. In terms of motor development, there was a significant improvement in activities of daily living, participation levels in school and leisure activities during free time, and an expanded range of motion. In terms of quality of life and well-being, adolescents with CP showed significant enhancements in self-confidence and self-esteem, significant relief from (spastic) pain, and improvements in social well-being and acceptance. ConclusionThis systematic review has synthesized the evidences of benefits of exercise rehabilitation and adapted physical activity on the psychomotor skills, motor abilities and motor development of children and adolescents with spastic CP. In terms of psychomotor skills, exercise rehabilitation and adapted physical activity help to improve the cognitive and motor skills of adolescents with spastic CP. In terms of motor abilities, exercise rehabilitation and adapted physical activity can improve muscle-related functions, gait and walking abilities, as well as balance and coordination. In terms of motor development, exercise rehabilitation and adapted physical activity significantly enhance activities of daily living and the level of participation in leisure physical activities. Finally, exercise rehabilitation and adapted physical activity can increase energy and motivation, alleviate pain, and enhance social well-being and acceptance.

Movement disorders in hereditary spastic paraplegias / Distúrbios de movimento em paraplegia espástica hereditária

Abstract Background Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia. Objective To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases. Methods We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022. Results Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia. Conclusion Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

Resumo Antecedentes As paraplegias espásticas hereditárias ou familiares (SPG) compreendem um grupo de doenças geneticamente e fenotipicamente heterogêneas caracterizadas por degeneração progressiva dos tratos corticospinais. As formas complicadas evoluem com vários outros sinais e sintomas neurológicos, incluindo distúrbios do movimento e ataxia. Objetivo Resumir as descrições clínicas de SPG que se manifestam com distúrbios do movimento ou ataxias para auxiliar o clínico na tarefa de diagnosticar essas doenças. Métodos Realizamos uma revisão da literatura, incluindo relatos de casos, séries de casos, artigos de revisão e estudos observacionais publicados em inglês até dezembro de 2022. Resultados O parkinsonismo juvenil ou de início precoce com resposta variável à levodopa foi relatado principalmente em SPG7 e SPG11. A distonia pode ser observada em pacientes com SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 e SPG76. O tremor não é um achado frequente em pacientes com SPG, mas é descrito em diferentes tipos de SPG, incluindo SPG7, SPG9, SPG11, SPG15 e SPG76. A mioclonia é raramente descrita em SPG, afetando pacientes com SPG4, SPG7, SPG35, SPG48 e SPOAN (paraplegia espástica, atrofia óptica e neuropatia). SPG4, SPG6, SPG10, SPG27, SPG30 e SPG31 podem raramente apresentar ataxia com atrofia cerebelar. E SPG autossômico recessivo, como SPG7 e SPG11, também pode apresentar ataxia. Conclusão Indivíduos com SPG podem apresentar diferentes formas de distúrbios do movimento, como parkinsonismo, distonia, tremor, mioclonia e ataxia. O distúrbio específico do movimento na manifestação clínica de um paciente com SPG pode ser uma pista clínica para o diagnóstico.

Distribución geográfica y tipo de infección del virus linfotrópico T humano en pacientes peruanos 2019-2021

En el presente estudio describimos y caracterizamos la distribución geográfica de los casos positivos confirmados a HTLV-1 y 2 de pacientes peruanos con diagnóstico presuntivo entre 2019 y 2021. De un total de 555 muestras positivas confirmadas, 546 (98,4%) fueron HTLV-1 y 9 (1,6%) HTLV-2. Además, 22 de 24 departamentos del Perú presentaron casos de HTLV-1, siendo los principales motivos de solicitud de confirmación diagnóstica: aspirante a donar sangre con prueba de tamizaje reactivo, sospecha de leucemia/linfoma y paraparesia espástica tropical. Los resultados reflejan que la identificación de los puntos críticos constituye una brecha persistente respecto al diagnóstico, siendo cruciales para reducir el número de nuevos casos en Perú.

In the present study we describe and characterize the geographic distribution of HTLV-1 and 2 positive cases from Peruvian patients with presumptive diagnosis 2019 - 2021. Of a total of 555 confirmed positive samples, 546 (98.4%) were HTLV-1 and 9 (1.6%) HTLV-2. In addition, 22 of 24 departments of Peru presented cases of HTLV-1. The main reasons for requesting a confirmatory diagnosis being: aspiring to donate blood with a reactive screening test, suspicion of leukemia/ lymphoma and tropical spastic paraparesis. The results reflect that the identification of critical points constitutes a persistent gap regarding the diagnosis, being crucial to reduce the number of new cases in Peru.

Elderly people with human T-cell leukemia virus type 1-associated myelopathy present an early impairment in cognitive skills / Idosos com mielopatia associada ao vírus da leucemia de células T humanas tipo 1apresentam comprometimento precoce em habilidades cognitivas

Abstract Background Cerebral changes occur in individuals with human T-cell leukemia virus type 1 (HTLV-1 )-associated myelopathy (HAM) and seem to predominate in subcortical areas. Little is known about the cognitive decline in the elderly living with HTLV-1. Objective To evaluate the cognitive aging of individuals infected with HTLV-1 aged ≥ 50 years. Methods This is a cross-sectional study of former blood donors infected with HTLV-1 who have been followed in the cohort of the Interdisciplinary Research Group on HTLV-1 since 1997. The groups of study consisted of 79 HTLV-1 infected individuals aged ≥ 50 years, with 41 of them presenting symptomatic HAM and 38 being asymptomatic carriers, and 59 seronegative individuals (controls) aged ≥ 60 years. All were submitted to the P300 electrophysiological test and neuropsychological tests. Results Individuals with HAM presented delayed P300 latency in relation to the other groups, and this latency delay increased progressively with aging. The performance of this group in the neuropsychological tests was also the worst. The HTLV-1- asymptomatic group performance was similar to that of the control group. Conclusions Individuals with HAM presented cognitive decline that progressed with aging and, although HTLV-1-asymptomatic carriers appear to present cognitive aging similar to that of healthy elderly people, concern about a subclinical cognitive impairment is warranted in this population.

Resumo Antecedentes Alterações cerebrais ocorrem em indivíduos com mielopatia associada ao vírus da leucemia de células T humanas tipo 1 (HTLV-1) (HAM) e parecem predominar em áreas subcorticais. Pouco se sabe sobre o declínio cognitivo em idosos vivendo com HTLV-1. Objetivo Avaliar o envelhecimento cognitivo de indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos. Métodos Trata-se de um estudo transversal com ex-doadores de sangue infectados pelo HTLV-1 acompanhados na coorte do Grupo Interdisciplinar de Pesquisa em HTLV-1 há 20 anos. Os grupos de estudo foram compostos por 79 indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos, sendo que 41 apresentavam HAM e 38 eram portadores assintomáticos, e 59 indivíduos soronegativos (controles) com idade ≥ 60 anos. Todos foram submetidos ao teste eletrofisiológico P300 e testes neuropsicológicos. Resultados Indivíduos com HAM apresentaram atraso na latência do P300 em relação aos demais grupos, e esse atraso de latência aumentou progressivamente com o envelhecimento. O desempenho desse grupo nos testes neuropsicológicos também foi o pior. O desempenho do grupo HTLV-1- assintomático foi semelhante ao do grupo controle. Conclusão Indivíduos com HAM apresentaram declínio cognitivo que progrediu com o envelhecimento e, embora os portadores assintomáticos do HTLV-1 pareçam apresentar envelhecimento cognitivo semelhante ao dos idosos saudáveis, justificase a preocupação com um comprometimento cognitivo subclínico nessa população.

Impaired flexibility in patients with tropical spastic paraparesis/HTLV-associated myelopathy: evaluation via pendulum fleximeter / Flexibilidade prejudicada em pacientes com paraparesia espástica tropical/mielopatia associada ao HTLV: avaliação via flexímetro pendular

Abstract Background Flexibility is crucial to the harmonious execution of joint movements. While skeletal muscle dysfunction in patients with HTLV-1 can interfere with mobility, it is unclear whether these patients experience reduced flexibility. Objective To evaluate the differences in flexibility between HTLV-1-infected individuals with and without myelopathy compared with uninfected controls. We also investigated whether age, sex, body mass index (BMI), physical activity level, or lower back pain influence flexibility in HTLV-1-infected individuals. Methods The sample consisted of 56 adults, of which 15 did not have HTLV-1, 15 had HTLV-1 without myelopathy, and 26 had TSP/HAM. Their flexibility was assessed using the sit-and-reach test and a pendulum fleximeter. Results No differences in flexibility were observed between the groups with and without myelopathy and controls without HTLV-1 infection using the sit-and-reach test. The pendulum fleximeter results of individuals with TSP/HAM presented the lowest flexibility among the groups with respect to trunk flexion, hip flexion and extension, knee flexion, and ankle dorsiflexion, even after adjusting for age, sex, BMI, level of physical activity, and lower back pain using multiple linear regression models. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced flexibility in movements: knee flexion, dorsiflexion, and ankle plantar flexion. Conclusions Individuals with TSP/HAM demonstrated reduced flexibility in most of the movements evaluated by the pendulum fleximeter. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced knee and ankle flexibility, potentially representing a marker of myelopathic development.

Resumo Antecedentes A flexibilidade é fundamental para a execução harmoniosa dos movimentos articulares. Embora a disfunção do músculo esquelético em pacientes com HTLV-1 possa interferir na mobilidade, não está claro se esses pacientes apresentam flexibilidade reduzida. Objetivo Avaliar as diferenças de flexibilidade entre os indivíduos infectados com e sem mielopatia e o grupo controle sem infecção HTLV-1. Também investigamos se idade, sexo, índice de massa corporal (IMC), nível de atividade física ou dor lombar influenciam a flexibilidade em indivíduos infectados pelo HTLV-1. Métodos A amostra foi composta por 56 adultos, dos quais 15 não possuíam HTLV-1, 15 possuíam HTLV-1 sem mielopatia e 26 possuíam TSP/HAM. A flexibilidade foi avaliada por meio do teste de sentar e alcançar e do flexímetro de pêndulo. Resultados Não foram observadas diferenças na flexibilidade entre os grupos com e sem mielopatia no teste de sentar e alcançar. Os resultados do flexímetro pendular dos indivíduos com TSP/HAM apresentaram a menor flexibilidade entre os grupos em relação à flexão do tronco, flexão e extensão do quadril, flexão do joelho e dorsiflexão do tornozelo, mesmo após ajuste para idade, sexo, IMC, nível de atividade física e dor lombar usando modelos de regressão múltipla linear. Além disso, os indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade nos movimentos de flexão do joelho, dorsiflexão e flexão plantar do tornozelo. Conclusão Indivíduos com TSP/HAM demonstraram redução da flexibilidade na maioria dos movimentos avaliados pelo flexímetro pendular. Além disso, indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade do joelho e tornozelo, representando potencialmente um marcador de desenvolvimento mielopático.

Case Study of Ayurvedic Management of Spastic Cerebral Palsy

Cerebral palsy is a group of permanent, non-progressive motor impairment syndromes secondary to lesions or anomalies of the brain arising in the early stages of its development. It has a high prevalence rate of 2- 3 per 1000 children. Among the various types, spastic cerebral palsy remains the most common, affecting about 61% of all people with cerebral palsy. In Ayurveda, this could be taken as a Vata predominant condition and included as Sarvangavata. Vatavyadhi treatment like Snehana, Swedana, Shodana and Brimhana, along with supportive therapies could give wonderful results. An 8 ½-year-old boy, a known case of post meningeal hydrocephalus with spastic cerebral palsy was treated in the In-Patient Department of Government Ayurveda College, Thiruvananthapuram. He was treated based on the principle of Vatavyadhi chikitsa with various Ayurvedic medicines internally and appropriate Panchakarma procedures, along with physiotherapy and speech therapy. He has been assessed before and after the treatment using the Modified Ashworth Scale and Barthel Index, and noticeable improvement has been got. Here spastic cerebral palsy was managed solely using Ayurveda medicines, the apt Panchakarma procedures and supportive therapies. Significant improvements in the quality of life of the child was seen. Ayurveda treatments along with supportive therapies are highly effective in managing spastic cerebral palsy, thereby imparting a better standard of living.

ATAD3A gene variations in a family with Harel-Yoon syndrome / 浙江大学学报·医学版

An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties. The laboratory results indicated hyperlactatemia, elevated markers of myocardial injury and inflammation, and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry. Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy. Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup (p.T498Nfs*13) and c.1376T>C (p.F459S) in the ATAD3A gene, inherited from their father and mother, respectively. The diagnosis of Harel-Yoon syndrome was confirmed. The proband and her sister were born with clinical manifestations of metabolic acidosis, hyperlactatemia, feeding difficulties, elevated markers of myocardial injury as well as cardiac insufficiency, and both died in early infancy.

Efficacy and mechanism of scalp acupuncture for spastic cerebral palsy / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of scalp acupuncture for spastic cerebral palsy (CP), and to explore its possible mechanism based on brain white matter fiber bundles, nerve growth related proteins and inflammatory cytokines.@*METHODS@#A total of 90 children with spastic CP were randomly divided into a scalp acupuncture group and a sham scalp acupuncture group, 45 cases in each group. The children in the two groups were treated with conventional comprehensive rehabilitation treatment. The children in the scalp acupuncture group were treated with scalp acupuncture at the parietal temporal anterior oblique line, parietal temporal posterior oblique line on the affected side, and parietal midline. The children in the sham scalp acupuncture group were treated with scalp acupuncture at 1 cun next to the above point lines. The needles were kept for 30 min, once a day, 5 days a week, for 12 weeks. Before and after treatment, the diffusion tensor imaging (DTI) indexes of magnetic resonance (FA values of corticospinal tract [CST], anterior limb of internal capsule [ICAL], posterior limb of internal capsule [ICPL], genu of internal capsule [ICGL], genu of corpus callosum [GCC], body of corpus callosum [BCC] and splenium of corpus callosum [SCC]), serum levels of nerve growth related proteins (neuron-specific enolase [NSE], glial fibrillary acidic protein [GFAP], myelin basic protein [MBP], ubiquitin carboxy terminal hydrolase-L1 [UCH-L1]) and inflammatory cytokines (interleukin 33 [IL-33], tumor necrosis factor α [TNF-α]), cerebral hemodynamic indexes (mean blood flow velocity [Vm], systolic peak flow velocity [Vs] and resistance index [RI], pulsatility index [PI] of cerebral artery), surface electromyography (SEMG) signal indexes (root mean square [RMS] values of rectus femoris, hamstring muscles, gastrocnemius muscles, tibialis anterior muscles), gross motor function measure-88 (GMFM-88) score, modified Ashworth scale (MAS) score, ability of daily living (ADL) score were observed in the two groups. The clinical effect of the two groups was compared.@*RESULTS@#After treatment, the FA value of each fiber bundle, Vm, Vs, GMFM-88 scores and ADL scores in the two groups were higher than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were higher than those in the sham scalp acupuncture group (P<0.05). After treatment, the serum levels of NSE, GFAP, MBP, UCH-L1, IL-33, TNF-α as well as RI, PI, MAS scores and RMS values of each muscle were lower than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were lower than those in the sham scalp acupuncture group (P<0.05). The total effective rate was 95.6% (43/45) in the scalp acupuncture group, which was higher than 82.2% (37/45) in the sham scalp acupuncture group (P<0.05).@*CONCLUSION@#Scalp acupuncture could effectively treat spastic CP, improve the cerebral hemodynamics and gross motor function, reduce muscle tension and spasticity, and improve the ability of daily life. The mechanism may be related to repairing the white matter fiber bundles and regulating the levels of nerve growth related proteins and inflammatory cytokines.

Effect of orthopedic elastic bandages on gait symmetry and walking ability in children with spastic hemiplegic cerebral palsy / 中国康复理论与实践

ObjectiveTo investigate the short-term efficacy of orthopedic elastic bandages on gait symmetry and walking ability in children with spastic hemiplegic cerebral palsy. MethodsFrom June, 2020 to June, 2023, 31 children with spastic hemiplegic cerebral palsy from Beijing Bo'ai Hospital were randomly divided into control group (n = 15) and experimental group (n = 16). Both groups received routine rehabilitation, while the control group received routine walking training, and the experimental group wore an orthopedic elastic bandage for walking training, for four weeks. The indexes of gait symmetry of foot deviation angle ratio (affected/healthy), step length ratio (affected/healthy), gait line ratio (affected/healthy) and standing stage ratio (affected percentage/healthy percentage) were calculated before and after training, and they were measured step width and the optional and maximum walking speed of 10-meter walk test (10MWT). ResultsOne case dropped off in the experimental group. After training, the foot deviation ratio, step length ratio, gait line ratio, and standing stage ratio improved in both groups (|t| > 2.434, P < 0.05), and they were better in the experimental group than in the control group (|t| > 2.230, P < 0.05); while the optional and maximum walking speed of 10MWT improved in both groups (|t| > 9.186, P < 0.001), and they were better in the experimental group than in the control group (|t| > 2.278, P < 0.05). ConclusionWearing orthopedic elastic bandages during rehabilitation can promote the gait symmetry and walking ability of children with spastic hemiplegic cerebral palsy.

Clinical analysis of a family with autosomal recessive spastic paraplegia caused by IBA57 gene mutations / 中华神经科杂志

Objective:To investigate the clinical, imaging and gene variation characteristics of hereditary spastic paraplegia type 74 caused by mutations in IBA57 gene. Methods:A retrospective analysis was performed on 2 cases of autosomal recessive spastic paraplegia caused by mutations in IBA57 gene who visited the Department of Neurology, the Affiliated Wuxi Children′s Hospital of Nanjing Medical University in 2010 and 2021, and the patients′ clinical data were collected. Results:The 2 patients were siblings with onset age of 4 years and 7 months, 1 year and 3 months, respectively. The same compound heterozygous mutations in IBA57 gene were found in the sibling patients [c.473G>C (p.R158P) and c.697C>T (p.R233X)]. Both patients were diagnosed as spastic paraplegia type 74. They had mild to moderate gait abnormalities, optic atrophy, decreased vision, and leukodystrophy with periventricular white matter abnormality, but no obvious growth and mental retardation in developmental assessment. Conclusions:Cases of spastic paraplegia type 74 caused by compound heterozygous mutations in IBA57 gene mainly manifested as childhood onset and slowly progressive inferior spasmodic weakness. The patients did not display significant cognitive impairment, and imaging examinations showed obvious leukodystrophy.

Dysarthria in hereditary spastic paraplegia type 4

Abstract Objective: To describe the speech pattern of patients with hereditary Spastic Paraplegia type 4 (SPG4) and correlated it with their clinical data. Methods: Cross-sectional study was carried out in two university hospitals in Brazil. Two groups participated in the study: the case group (n = 28) with a confirmed genetic diagnosis for SPG4 and a control group (n = 17) matched for sex and age. The speech assessment of both groups included: speech task recording, acoustic analysis, and auditory-perceptual analysis. In addition, disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Results: In the auditory-perceptual analysis, 53.5% (n = 15) of individuals with SPG4 were dysarthric, with mild to moderate changes in the subsystems of phonation and articulation. On acoustic analysis, SPG4 subjects' performances were worse in measurements related to breathing (maximum phonation time) and articulation (speech rate, articulation rate). The articulation variables (speech rate, articulation rate) are related to the age of onset of the first motor symptom. Conclusion: Dysarthria in SPG4 is frequent and mild, and it did not evolve in conjunction with more advanced motor diseases. This data suggest that diagnosed patients should be screened and referred for speech therapy evaluation and those pathophysiological mechanisms of speech involvement may differ from the length-dependent degeneration of the corticospinal tract.

Hereditary spastic paraplegia due to nipa1 gene mutation: case report

ABSTRACT Introduction: Hereditary spastic paraplegia (HSP) is the term for a group of neurological disorders characterized by progressive spasticity and muscle weakness in the lower limbs. Its etiology is genetic and has been associated with mutations in more than 60 genes. HSP is rare and may be useful in the differential diagnosis of cerebral palsy. Case presentation: 16-year-old male with a diagnosis of HSP due to mutation of the NIPAi gene:c.316G>A (p. Gly106arg), which corresponds to HSP type 6 (SPG6). The patient presented with clinical signs of progressive upper motor neuron syndrome in the lower limbs, such as spasticity, hyperreflexia and paraparesis, associated with focal onset seizures diagnosed at age 11 and successfully treated with valproic acid. Spasticity treatment was complex and included oral baclofen, intraoperative botulinum toxin, physical therapy, and multilevel orthopedic surgery for the management of musculoskeletal deformities. Conclusion: This is a rare case of complex HSP, associated with epilepsy, due to the mutation of the NIPAi gene (SPG6), the most common pathogenic variant within this type of mutation. The present case demonstrates the importance of making an early diagnosis of GSP6 to perform timely interventions in these patients, prevent complications, and avoid a higher level of disability.

RESUMEN Introducción. La paraplejía espástica hereditaria (PEH) es un grupo de trastornos neurológicos caracterizados por espasticidad progresiva y debilidad muscular de miembros inferiores. Su etiología es genética y se ha asociado con mutaciones en más de 60 genes. La PEH es poco frecuente y puede ser útil en el diagnóstico diferencial de la parálisis cerebral. Presentación de caso. Adolescente masculino de 16 años con diagnóstico de PEH por mutación del gen NIPAi: c. 316G>A (p. Gly106arg), correspondiente a una PEH tipo 6 (SPG6). El paciente presentó signos clínicos de síndrome de motoneurona superior progresivos en miembros inferiores como espasticidad, hiperreflexia y paraparesia, asociados a epilepsia de inicio focal diagnosticada a los 11 años y tratada satisfactoriamente con ácido valproico. El manejo de la espasticidad fue complejo e incluyó baclofeno oral, toxina botulínica intraoperatoria, terapia física y cirugía ortopédica multinivel para manejo de deformidades musculoesqueléticas en miembros inferiores. Conclusión. El presente caso demuestra la importancia de realizar un diagnóstico temprano de la SPG6 (variante más común de la PEH) para realizar intervenciones oportunas en estos pacientes, prevenir complicaciones y evitar un mayor nivel de discapacidad.

Spastic ataxia type 8 with a homozygous mutation of the NKX6-2 gene: a case report and literature review / 中华实用儿科临床杂志

NKX6-2 encodes a transcription factor involving the genesis and development of oligodendrocytes.Mutations in the NKX6-2 gene are related to a severe variant of hypomyelinating leukodystrophy, namely the NKX6-2-related spastic ataxia type 8 (SPAX8). As of March 24, 2020, there are 36 cases of SPAX8 involving 11 mutations of the NKX6-2 gene, which has not been reported in Chinese population.This article for the first time reported a 31-month-old Chinese boy diagnosed as SPAX8 caused by a novel mutation of the NKX6-2 gene at c. 234dup(p.Leu79Alafs*? ) admitted to the Department of Rehabilitation, Guangdong Women and Children Hospital in October 2019 retrospectively.He presented severe global psychomotor delay, spasticity, nystagmus, hearing impairment and trichiasis, ametropia of both eyes, and retinal degeneration of the right eye, which have not been reported in previous cases.His elder sister presented relevant manifestations, but did not perform the genetic testing.Through this case report and literature review, the genotype and phenotype of SPAX8 were expanded.

Clinical phenotype and genotype analysis of hereditary spastic paraplegia type 35 / 中华神经科杂志

Objective:To report 8 cases of hereditary spastic paraplegia type 35 (SPG35) in Chinese mainland, summarize the clinical and genetic features of this disease.Methods:Eight probands with SPG35, admitted in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2006 to June 2021, were collected in detail. Physical examination, cranial imaging examination and whole exome sequencing were conducted, followed by Sanger sequencing and family co-segregation. In addition, the recent advances in clinical, genetic and pathogenesis studies of the disease were also reviewed.Results:Among all of the 8 patients, 7 had juvenile-onset and 1 was adult-onset. The clinical phenotype of 2 cases was pure spastic paraplegia. The other 6 cases presented with complicated form, which was characterized by not only motor dysfunction, but also cognitive impairment and dysphagia, etc. Genetic testing revealed a total of 13 fatty acid 2-hydroxylase (FA2H) gene (NM_024306) mutations, of which 6 were reported and 7 were newly reported in this study.Conclusions:SPG35 is an autosomal recessive neurodegenerative disease with highly phenotypic heterogeneity, with the causative gene as FA2H. The genotype-phenotype correlations in SPG35 are not clear.

Analysis of pathogenic genes in two cases of Sj?gren-Larsson syndrome / 中华皮肤科杂志

Objective:To detect pathogenic mutations in 2 patients with Sj?gren-Larsson syndrome.Methods:Clinical data were collected from 2 children with Sj?gren-Larsson syndrome, who were diagnosed and treated in Department of Dermatology, Capital Institute of Pediatrics, and genetic testing was performed to clarify their pathogenic mutations.Results:Both the 2 patients presented with typical ichthyosis-like skin manifestations, accompanied by a certain degree of intellectual disorder and growth, development and motor retardation. A previously reported homozygous mutation c.1157A>G was identified in the ALDH3A2 gene in case 1; compound heterozygous mutations c.1157A>G and c.1309A>T were identified in the ALDH3A2 gene in case 2, which were considered as novel pathogenic mutations.Conclusion:Genetic testing should be performed as early as possible in patients with suspected Sj?gren-Larsson syndrome, in order to facilitate early definite diagnosis.

A novel mutation of SPAST gene in a hereditary spastic paraplegia type 4 family / 中华内科杂志

Objective:To clarify the pathogenicity and further explore the association between genotype and clinical phenotype of this variant, analyzing a novel variation of SPAST gene in hereditary spastic paraplegia (HSP) family from Changzhi city, Shanxi Province.Methods:A family with HSP was tracked and collected in Neurology Department of Heping Hospital Affiliated to Changzhi Medical College in October 2019. Peripheral venous blood of 2 ml was extracted from the proband and 8 other members of the family, genomic DNA was extracted from the blood samples, and the genes of spastic paraplegia were screened by next-generation sequencing (NGS). HGMD, 1000G, OMIM databases and PolyPhen2, SIFT and other software were used for bioinformatics analysis of suspected mutations. Multiplex ligation-dependent probe amplification (MLPA) was used to further screen for total deletions/duplications in patients who remained negative after targeting NGS, and Sanger sequencing was performed to verify the suspected pathogenic mutation sites in the family to determine co-isolation of the mutation sites in the family members. Finally, it is necessary to refer to the latest version of The American College of Medical Genetics and Genomics (ACMG) sequence variation interpretation guidelines to interpret the mutation sites to determine pathogenicity.Results:The HSP family consist 47 members of 4 generations and 10 patients, with onset ages ranging from 2 to 44 years. The proband′s daughter only showed positive bilateral Babbitt signs on physical examination, and the rest of the patients showed spasticity and weakness of lower limbs with varying severity on this basis. Preliminary screening by next-generation sequencing technology showed that the proband had frame-shift variation of SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) and missense variation of DCTN1 gene c.2213A>G (p.Gln738Arg). Then, Sanger sequencing was used for in-family verification, which showed SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) was detected in the affected members include father, brother, son and daughter, and not detected in the unaffected normal members, the proband′s wife, mother, sister and sister-in-law. However, the unaffected of mother detected missense variation of DCTN1 gene c.2213A>G (p.Gln738Arg), while the remaining members did not detect this variation. The results of MLPA showed that no large fragment variation was found.Conclusions:The genetic pattern of the HSP family was autosomal dominant, and the clinical characteristics were consistent with hereditary spastic paraplegia type 4 (SPG4). Co-segregation of SPAST gene c.1057_1058insCC (p.Leu354HisfsTer11) was found in the HSP family and was the pathogenicity cause of this SPG4 family, and it was a newly discovered mutation locus.

Effects of dual-task treadmill training on motor function of children with spastic hemiplegic cerebral palsy / 中华实用儿科临床杂志

Objective:To investigate the influence of dual-task treadmill training on the motor function of children with spastic hemiplegic cerebral palsy(CP).Methods:A prospective study was carried out on 36 children with spastic hemiplegic CP admitted to the Department of Rehabilitation, Qingdao Women and Children′s Hospital from March 2020 to August 2021.The subjects were divided into the control group (18 cases) and the experimental group (18 cases) by the random number sequence method.During the intervention, 2 cases in the control group dropped out of the study due to cough and fever.Finally, there were 16 cases left in the control group and 18 cases in the experimental group.Both groups received the same routine rehabilitation training.Additionally, the control group were given single-task treadmill training, while the experimental group were treated dual-task treadmill training.Before training and after 4 weeks of training, the children in the two groups were evaluated and compared by using Gross Motor Function Measure-88 (GMFM-88), Pediatric Balance Scale (PBS), Maximum Walking Speed test(MWST), single-task modified Timed Up and Go test (mTUG) and dual-task mTUG.Gender and Gross Motor Function Classification System(GMFCS) classification in general data were compared by using the Chi-square test or Fisher′ s exact test.Age and indices of rehabilitation assessment were compared by using the paired-samples t-test within groups and indepen-dent-samples t-test between the two groups. Results:There was no significant difference in the evaluation data of the GMFM-88 D score [(34.25±1.61) points vs.(34.56±1.76) points], GMFM-88 E score [(50.53±7.20) points vs. (50.61±6.75) points], PBS score [(39.06±4.34) points vs. (38.89±4.44) points], MWST time [(12.69±3.07) s vs. (13.56±2.97) s], single-task mTUG time [(11.38±2.58) s vs. (11.94±2.51) s], and dual-task mTUG time [(30.06±8.08) s vs. (31.50±8.56) s]between the control group and the experimental group before training (all P>0.05). After 4 weeks of training, the GMFM-88 score of the control group was (35.88±1.82) points in the D dimension and (51.20±6.64) points in the E dimension.Besides, the PBS score of the control group was (40.75±4.14) points, the MWST time was (10.81±2.95) s, and the single-task mTUG time was (10.06±2.52) s. As for the experimental group, the GMFM-88 score was (36.28±1.99) points in the D dimension and (53.94±6.98) points in the E dimension, the PBS score was (43.06±4.94) points, the MWST time was (10.44±2.83) s, and the single-task mTUG time was (10.56±2.73) s. The evaluation indexes of the two groups after training for 4 weeks were significantly better than those before training ( t=-3.058, -2.197, -7.132, 1.235, 2.952 in the control group, and t=-5.953, -12.432, -8.333, 3.149, 7.578 in the experimental group, all P<0.05). There was no significant difference in GMFM-88 scores in D and E dimensions, PBS scores, MWST time and single-task mTUG time between the two groups ( P>0.05). The dual-task mTUG time of the control group was (29.10±8.28) s after 4 weeks of training, which was not statistically different from that before training ( t=1.578, P>0.05). The dual-task mTUG time of the experimental group was (23.06±7.30) s after 4 weeks of training, which was significantly better than that before training ( t=13.930, P<0.05) and that of the control group ( t=2.296, P<0.05). Conclusions:Both single-task and dual-task treadmill training can remarkably improve the motor function of children with spastic hemiplegic CP.Single-task training cannot improve the motor function of children with spastic hemiplegic CP in the dual-task condition, while dual-task training can effectively improve the motor function with spastic hemiplegic CP in the dual-task condition.

Advances in treatment of hereditary spastic paraplegia / 国际儿科学杂志

Hereditary spastic paraplegia (HSP) is a neurodegenerative disease with clinical manifestations of increased muscle tone, enhanced tendon reflex and positive pathological reflex of both lower limbs.Currently, the pathological mechanism of HSP is considered as bilateral corticospinal axonal degeneration.So far, more than 80 pathogenic genes have been reported to be associated with the pathogenesis of HSP, among which spastic paraplegia type 4 (SPG4) caused by SPAST mutation is the most common.Genetic testing is crucial for diagnosing and typing HSP.The incidence of this disease is low.Although it is not a short-term fatal disease, it will seriously affect the patient′s self-care ability and cause seriously psychological burden to the patient with the progress of the disease.There is no effective cure for the disease at present.In this paper, the therapeutic methods of HSP are reviewed from different aspects: small molecular compounds, gene therapy, rehabilitation therapy and surgical treatment.

Assessment of Postoperative Surface Electromyography and Joint Angle in Children with Spastic Cerebral Palsy / 医用生物力学

Objective To analyze and assess the postoperative motor function in children with spastic cerebral palsy (SCP) by surface electromyography (sEMG) and joint angle. Methods Sixteen children with SCP were involved in this study. The sEMG of rectus femoris, biceps femoris, semitendinosus, tibialis anterior, lateral gastrocnemius and medial gastrocnemius muscles and joint angles of the hip, knee and ankle during straight walking were collected preoperatively and postoperatively. In every gait phase, the mean values of joint angles, root mean square and integrated electromyography of sEMG were calculated, to evaluate muscle strength and muscular tension quantitatively. Results The muscle tension of lower limbs was significantly decreased (P<0.05). The muscle strength of rectus femoris and biceps femoris was decreased in the swing phase. At the midswing and terminal swing phase, the strength of tibialis anterior increased significantly (P<0.05). The flexion angle of hip and knee decreased significantly (P<0.05). The dorsiflexion angle of ankle increased significantly (P<0.05), and the varus angle decreased significantly (P<0.05). Conclusions After operation, the crouching gait and clubfoot were improved positively. Therefore, the motor function of children was improved. Combining sEMG and joint angle can evaluate the muscle function of patients quantitatively, and it also can provide references for clinical diagnosis.

Family-centered task-oriented training can significantly improve the functional independence and life quality of children with spastic cerebral palsy / 中华物理医学与康复杂志

Objective:To observe the effect of a family-centered task-oriented training (TOT) program on the functional independence and life quality of children with spastic cerebral palsy.Methods:A total of 62 children with spastic cerebral palsy were randomly divided into a control group ( n=31) and a TOT group ( n=31). The children in the control group were given family rehabilitation training according to the discharge instruction manual, while the children in the TOT group received family-centered TOT. Both groups trained for 1 hour once a day, 5 days a week for 6 months. The mobility, functional independence and life quality of the two groups were evaluated with the pediatric evaluation of disability inventory (PEDI), functional independence measures for Chinese children (WeeFIM) and a pediatric quality of life inventory (PedsQL) before and after 3 and 6 months of treatment. Results:After 6 months there was significant improvement in the average mobility, WeeFIM and PedsQL scores of both groups. The average mobility, WeeFIM and PedsQL scores of the TOT group were then significantly better than those of the control group.Conclusion:Family-centered TOT training can significantly improve the functional independence and life quality of children with spastic cerebral palsy.