Objective:To investigate the clinical phenotype and genetic variation of Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS), and to enhance clinicians′ knowledge of the disease.Methods:The clinical data of a child with BVSYS admitted to the Department of Neurological Rehabilitation, Qingdao Women and Children′s Hospital Affiliated to Qingdao University in February 2023 were collected. Whole genome sequencing was used to analyze the pathogenic genes of the child, and Sanger sequencing was used to verify the suspected mutation sites of the family members. The clinical phenotype and genetic variation characteristics were analyzed, and the clinical characteristics of BVSYS were summarized in combination with relevant literature.Results:The patient, a female aged 3 years and 1 month, presented with global developmental delay, speech disorder, distinctive facial features, esotropia, epilepsy, hypotonia and atrial septal defect. Brain magnetic resonance imaging revealed bilateral ventriculomegaly with abnormal signal intensity in the posterior bodies of both lateral ventricles and thinning of the corpus callosum. The whole genome sequencing revealed a homozygous missense mutation c.518 (exon5) T>C (p.IIe173Thr) in the MED25 gene of the child, and Sanger sequencing confirmed that her parents and elder brother carried the aforementioned heterozygous mutation, which was classified as a likely pathogenic mutation according to the guidelines of the American College of Medical Genetics and Genomics. A total of 22 cases from 6 literature sources were retrieved, with no reported cases in China so far. Conclusions:BVSYS is clinically rare. For patients presenting with unexplained global developmental delay or intellectual disability combined with craniofacial, neurological, cardiac, and eye abnormalities, targeted genetic testing can facilitate a definite diagnosis.

Objective:To summarize the clinical and genetic characteristics of early-onset spinocerebellar ataxia type 5 (SCA5) caused by SPTBN2 gene mutation. Methods:The clinical and genetic data of a child with early-onset SCA5 diagnosed in the Department of Children′s Rehabilitation, Women and Children′s Hospital Affiliated to Qingdao University in February 2022 were retrospectively analyzed. The literatures related to early-onset SCA5 in major databases at home and abroad were retrieved and summarized.Results:The patient, a 4 years and 1 month old girl, was admitted to hospital because of "unable to stand independently at 2 years and 3 months", primarily presented with developmental delay, ataxia, hypotonia, and tendon hyperreflexia during infancy. Progressive cerebellar atrophy was observed on brain magnetic resonance imaging. A de novo heterozygous mutation of the SPTBN2 c.793G>C(p.Asp265His) was identified in the patient. Following hospitalization, the child received comprehensive rehabilitation therapy encompassing physical, occupational, language, educational interventions as well as bicycle ergometer training and transcranial magnetic stimulation. The patient was followed-up for more than 1 year to 4 years and 1 month old, whose motor function, cognitive abilities, and language skills were improved to some extent. A total of 13 English articles and 1 Chinese article were retrieved from the databases. A total of 20 early-onset SCA5 patients have been reported, with onset ages all within 12 months. Infants exhibited decreased muscle tone and delayed motor milestones, with the main clinical manifestations of ataxia, generalized developmental delay, and cerebellar atrophy. The previously reported cases involved 11 mutation sites in the SPTBN2 gene, and the main types of mutations were de novo missense mutations. The mutation site in this case has not been reported in the previous literature. Conclusions:Early-onset SCA5 is a rare autosomal dominant disorder caused by heterozygous mutations in the SPTBN2 gene. The main clinical manifestations include ataxia from infancy, developmental retardation and cerebellar atrophy. Early rehabilitation intervention can improve the degree of the dysfunction.

Objective:To analyze the etiology and typology of cerebral palsy (CP) in preschool children with comorbid epilepsy, and their gross motor function (GMFCS) and cranial magnetic resonance (MRICS) classifications.Methods:A total of 837 children (aged 6 months to 6 years) hospitalized with cerebral palsy were divided into an epileptic group ( n=174) and a non-epileptic group ( n=663). Their general data, CP type, CP etiology, GMFCS classifications, MRICS classifications and Gesell development scores were analyzed. Results:Among the 174 children with epilepsy, 158 (90.8%) were under 3 years old. The most common type of CP in the epilepsy group was spastic quadriplegia (50.0%). In the non-epilepsy group it was spastic diplegia (42.1%), a significant difference. There were also significant differences between the two groups in terms of etiology. The number of cases of abnormal brain development differed significantly, as did genetic factors and history of asphyxia. There were also significant differences between the two groups in terms of GMFCS classifications and the distribution of MRICS classes. In the epileptic group, the proportion of gray matter injury was 31.6%. However, white matter injury ranked first in both the epileptic group and the non-epileptic group, reaching 40.8% and 53.7%, respectively. In terms of cognitive functioning there were significant differences in the groups′ mean Gesell developmental quotients: epileptic group 52.21 and non-epileptic group 70.59.Conclusions:The clinical characteristics of CP children with comorbid epilepsy differ with age, CP cause and type, as well as GMFCS and MRICS classifications. Children less than 3 years old with brain mal-developments and genetic factors or asphyxia-hypoxia etiology mostly display spastic quadriplegia CP. They mainly suffer from gray matter injury. The higher the GMFCS classification, the greater the proportion of CP with co-occurring epilepsy and the more severe the cognitive lag tends to be.

Objective:To explore any effect of the single- and dual-task treadmill training on the functioning of children with bilateral spastic cerebral palsy.Methods:Fifty children with bilateral spastic cerebral palsy were randomly divided into a single-task treadmill training group (the control group, n=25) and a dual-task treadmill training group (the observation group, n=25). All of the children also received routine rehabilitation training, and the control and observation groups also conducted single- and dual-task treadmill training in addition to the routine rehabilitation training, respectively. Before and after 2 months of treatment, each child′s gross motor functioning was quantified using sections D (standing) and E (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument. Balance was quantified using the Pediatric Balance Scale (PBS) and walking mobility was quantified using a 1 minute walking test (1MWT). Modified and dual task Timed Up and Go (mTUG) tests and dual-task effects (DTE) tests were also administered. Results:There were no significant differences in average test scores between the two groups before the treatment. After the treatment significant improvement was observed in both groups. There was no significant difference between the two groups in terms of average GMFM-88, PBS and 1MWT scores, but significantly greater improvement was observed in the average dual-task mTUG and DTE results of the observation group.Conclusion:Both single- and dual-task treadmill training are effective supplements to routine rehabilitation training for children with bilateral spastic cerebral palsy. Dual-task treadmill training is more effective than the single-task version.

Objective:To explore the effects of goals-activity-motor enrichment(GAME) therapy on the function of gross and fine motion in infants at high risk of cerebral palsy.Methods:Prospective study.A total of 116 children at high risk of cerebral palsy who met the inclusion criteria and were admitted to the Rehabilitation Department of Qingdao Women and Children′s Hospital from November 2017 to November 2019 were selected in a randomized, single-blind, controlled trial, and randomly divided into control group (58 cases) and observation group (58 cases) according to the random number table method.The two groups were then divided into mild group, moderate group and severe group according to the gross motor quotient(GMQ) of Peabody Motor Development Scale-2 (PDMS-2). During treatment, 4 cases of shedding occurred in the control group and 8 cases in the observation group, respectively.Finally, 54 cases were included in the control group and 50 cases in the observation group.The control group was given regular early intervention rehabilitation, whereas the observation group was given GAME treatment.The Gross Motor Function Measure-88 (GMFM-88), the GMQ of PDMS-2 and the fine motor quotient (FMQ) of PDMS-2 were used to assess the motor function of children before intervention and after 12 weeks of treatment.The Chi- square test or Fisher′ s exact test was used to compare gender-specific data, while the t-test was used to compare age-specific data and rehabilitation evaluation indices. Results:The GMFM-88 scores, GMQ, and FMQ of children in both groups improved significantly after treatment, and the difference was statistically significant [control group GMFM-88: (63.52±10.06) scores vs.(47.02±8.19) scores, t=-19.770, GMQ: 83.02±15.52 vs.73.56±14.72, t=-18.180, FMQ: 81.19±14.88 vs.71.22±13.92, t=-18.413, all P<0.05; observation group GMFM-88: (68.06±10.82) scores vs.(46.16±8.73) scores, t=-32.856, GMQ: 89.98±18.10 vs.72.94±13.84, t=-17.089, FMQ: 88.34±18.08 vs.72.26±13.74, t=-15.370, all P<0.05], and the GMFM-88, GMQ, and FMQ scores of the observation group were significantly higher than those of the control group after treatment, with statistically significant differences(GMFM-88: t=-2.176, GMQ: t=-2.111, FMQ: t=-2.210, all P<0.05). In the observation group, the added value score and quotient of mild group and moderate group were significantly increased compared with that of severe group, and the differences were statistically significant [GMFM-88 added value: the mild group (24.11±3.36) scores and moderate group (22.91±3.46) scores were compared with the severe group (15.70±4.08) scores, t=5.881, 5.164, all P<0.05, GMQ added value: the mild group (19.61±6.83) and moderate group (18.27±6.61) were compared with the severe group (9.80±4.29), t=4.098, 3.915, all P<0.05, the added value of FMQ: mild group (18.72±7.11) and moderate group (17.36±6.10) were compared with severe group (8.50±5.82), t=3.873, 3.863, all P<0.05]. Conclusions:GAME treatment is more effective than early rehabilitation training at improving gross and fine motor function in infants at high risk of cerebral palsy.Its benefits on mild and moderate infants at high risk of cerebral palsy are superior.

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.

Objective:To explore the effect of goals-activity-motor enrichment (GAME) intervention on the motor function of infants with a mild or moderate developmental disorder.Methods:Randomized, single-blind, controlled trials were applied. Totally 108 infants with mild-to-moderate developmental delay, aged 0 to 12 months, were randomly divided into an observation group and a control group, each of 54. Both groups were further divided into two subgroups, a less-than-6-month-old subgroup and a not-less-than-6-month-old subgroup. All of the children received 30 minutes of routine rehabilitation training five days a week and a 60-minute family intervention every day. In addition, the control group was given traditional neuro-developmental treatment (NDT) while the observation group was provided with an intervention based on the GAME program. Before and after 8 weeks of treatment, both groups were evaluated using the Alberta infant motor scale (AMIS).Results:After the intervention, both groups′ average total scores and average scores in the different positions were significantly better than before the intervention. The average AIMS scores of the observation group supine, prone and seated, as well as their average total score were significantly higher than those of the control group after the intervention. There were no significant differences in the AIMS score increases in the different positions between the two subgroups. However, the increase in average total AIMS score of the less-than-6-month-old subgroup was significantly greater than that of the older subgroup.Conclusion:The GAME protocol can improve the motor function of infants with mild to moderate developmental disorders more effectively than a traditional NDT program. The effect is greater with younger infants.

The enriched environment is an artificial environment for animal models of rodentia. In the enriched environment, model animals may improve synaptic plasticity, inhibit apoptisis and regulate autophage after hypoxic-ischemic brain damage, that promote the recovery.

Objective To explore the effects of environmental enrichment (EE) on learning and memory ability and the expression of brain-derived neurotrophic factor (BDNF) and synaptophysin in hippocampus of neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods Forty Wistar neonatal male rats aged 7 days were randomly divided into EE intervention for 6 hours(6 h EE) group (n =10),EE intervention for 12 hours (12 h EE) group (n =10),model group (n =10) and sham group (n =10).The first 3 groups were performed with HIBD.The 6 h EE and 12 h EE group received EE stimuli for 6 h and 12 h respectively,once a day for 14 days.Learning and memory of the rats were tested by using Morris water maze.The expression levels of BDNF and synaptophysin in hippocampus were determined with Western blot.Results The escape latency of all groups gradually reduced with the increase of training days,but there was no significant difference in the escape latency among the 4 groups (F =0.237,P ＞ 0.05).The rats in the 6 h EE group,12 h EE group and model group spent less time in the target quadrant and showed a significant reduction of BDNF and synaptophysin(6 h EE group:0.529 ± 0.038,0.889 ± 0.027;12 h EE group:0.660 ± 0.034,1.114 ± 0.037;model group:0.225 ± 0.015,0.672 ± 0.057) in the hippocampus compared with the sham group (0.803 ± 0.026,1.347 ± 0.092) (all P ＜ 0.01).In the 6 h EE group and 12 h EE group,the rats significantly increased the time spent in target quadrant and aggrandized the expression of BDNF and synaptophysin in hippocampus compared with the model group.Moreover,the 12 h EE group had a better performance than the 6 h EE group in the space exploration and the expression of BDNF and synaptophysin.Conclusion EE is helpful for improving learning and memory ability in neonatal rats with HIBD,which may be associated with up-regulating the expression of BDNF and synaptophysin in hippocampus.

Objective To explore the effect of environmental enrichment intervention on spatial memory function,expressions of phosphorylated cAMP response element binding protein (pCREB) and apoptotic regulated genes (Bcl-2 and Bax) in the hippocampus of immature rats with hypoxic-ischemic brain damage (HIBD).Methods Two kinds of raising environments were chosen:standard environment and environmental enrichment.Thirty-two Wistar rats aged 7 days were randomly divided into sham-operated group (n=10),environmental enrichment group (n=11) and standard environment group (n=11).Rats in both environmental enrichment group and standard environment group were induced animal models of HIBD using the way of Rice-Vannucci.Rats in the sham-operated group and standard environment group were raised in standard environment,while rats in the environmental enrichment group were raised in environmental enrichment.After 21 days of environmental enrichment intervention,the escape latency for searching the hidden platform of immature rats was detected by Morris water maze navigation test.The pCREB protein expression was detected by Western blotting;Bcl-2 and Bax expressions in the hippocampus were detected by immunohistochemisty.Results (1) On the fourth and fifth days of Morris water-maze test,the escape latency in the environmental enrichment group was shorter significantly as compared with that in the standard environment group (P＜0.05).(2) As compared with the lesion lateral hippocampus of standard environment group,the expressions ofpCREB (0.435±0.121 vs.0.756±0.101) and Bcl-2 (0.103±0.028 vs.0.165±0.017) in the lesion lateral hippocampus of environmental enrichment group were significantly higher (P＜0.05);however,the expression of Bax in the environmental enrichment group was statistically lower (0.402± 0.028 vs.0.325±0.019,P＜0.05).Conclusion Environmental enrichment intervention can improve the spatial memory ability in the hippocampus after HIBD,which indicates that the effectiveness of environmental enrichment intervention might be through the pathway of CREB-pCREB-apoptotic regulated genes (Bcl-2 and Bax).