[Clinical and genetic analyses of Joubert syndrome in children]. / 儿童Joubertç»¼åˆå¾ä¸´åºŠåŠé—ä¼ å­¦åˆ†æž.

OBJECTIVES: To study the clinical and genetic features of Joubert syndrome (JS) in children. METHODS: A retrospective analysis was performed on the clinical data, genetic data, and follow-up data of 20 children who were diagnosed with JS in the Department of Children's Rehabilitation, the Third Affiliated Hospital of Zhengzhou University, from January 2017 to July 2022. RESULTS: Among the 20 children with JS, there were 11 boys and 9 girls. The common clinical manifestations were developmental delay (20 children, 100%), abnormal eye movement (19 children, 95%), and hypotonia (16 children, 80%), followed by abnormal respiratory rhythm in 5 children (25%) and unusual facies (including prominent forehead, low-set ears, and triangular mouth) in 3 children (15%), and no limb deformity was observed. All 20 children (100%) had the typical "molar tooth sign" and "midline cleft syndrome" on head images, and 6 children (30%) had abnormal eye examination results. Genetic testing was performed on 7 children and revealed 6 pathogenic genes, i.e., the CPLANE1, RPGRIP1L, MKS1, CC2D2A, CEP120, and AHI1 genes. CONCLUSIONS: For children with developmental delay, especially those with abnormal eye movement and hypotonia, it is recommended to perform a head imaging examination to determine the presence or absence of "molar tooth sign" and "midline cleft syndrome", so as to screen for JS to avoid missed diagnosis and misdiagnosis. There are many pathogenic genes for JS, and whole-exome sequencing can assist in the diagnosis of JS.

[Effect of rehabilitation treatment based on the ICF-CY Core Sets on activities of daily living in children with cerebral palsy: a prospective randomized controlled study].

OBJECTIVE: To study the effect of rehabilitation treatment based on the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) Core Sets on activities of daily living in children with cerebral palsy. METHODS: The children with cerebral palsy were divided into an observation group (n=63) and a control group (n=59) using a random number table. The children in the observation group were evaluated using the brief ICF-CY Core Sets for children under 6 years to identify intervention targets and develop rehabilitation plans and goals, and then specific methods were selected for rehabilitation treatment. The children in the control group were evaluated and treated with the traditional rehabilitation mode. The scores of the Functional Independence Measure for Children (WeeFIM) and the Infants-Junior Middle School Students' Social-Life Abilities Scale were assessed for both groups before treatment and after three courses of treatment. The intervention of environmental factors was compared between the two groups. RESULTS: There was no significant difference in the scores of the WeeFIM and Social-Life Abilities scales between the two groups before treatment (P > 0.05). After treatment, both groups had significant increases in the scores of the WeeFIM and Social-Life Abilities scales (P < 0.001). The observation group had significantly higher scores of WeeFIM and Social-Life Abilities scales than the control group after treatment (P < 0.05). There was no significant difference in the use rate of orthosis between the two groups (P > 0.05), but the use rate of assistive devices for self-help, transfer and communication, the rate of facility renovation, and the rate of family rehabilitation guidance in the observation group were significantly higher than those in the control group (P < 0.05). CONCLUSIONS: The rehabilitation treatment regimen for cerebral palsy based on the CF-CY Core Sets pays more attention to the influence of environmental factors in the process of rehabilitation and can effectively improve the activities of daily living of children with cerebral palsy.

[Clinical effectiveness of Subjective Global Nutritional Assessment in hospitalized children with cerebral palsy].

OBJECTIVE: To investigate the nutritional status of children with cerebral palsy (CP) and the clinical effectiveness of Subjective Global Nutritional Assessment (SGNA) in nutritional assessment of hospitalized children with CP. METHODS: A total of 208 children with CP, aged 1-5 years, who were hospitalized from April to October 2019 were enrolled as subjects. SGNA was used to investigate nutritional status, and the Z-score method recommended by the World Health Organization was used as a reference standard to validate the clinical effectiveness of SGNA. RESULTS: The detection rate of malnutrition in children with CP was 42.3% by SGNA and 39.4% by the Z-score method (P>0.05). The application of SGNA showed high consistency between different evaluators (κ=0.621, P<0.001). With the Z-score method as the reference standard, SGNA had a sensitivity of 80.5%, a specificity of 82.5%, a positive predictive value of 75.0%, and a negative predictive value of 86.7%, and high consistency was observed between the two evaluation methods (κ=0.622, P<0.001). SGNA was moderately consistent with weight-for-age Z-score and height-for-age Z-score (κ=0.495 and 0.478 respectively, P<0.001) and was poorly consistent with weight-for-height Z-score (κ=0.197, P<0.05). CONCLUSIONS: There is a relatively high incidence rate of malnutrition in children with CP. SGNA can be used as a tool to assess the nutritional status of children with CP.

[Autosomal dominant intellectual disability-40 caused by a de novo mutation of the CHAMP1 gene: a case report].

A boy, aged 6 months, had the manifestations of intellectual and motor developmental delay, head instability, general weakness, unawareness of grasping objects by hands, and unusual facies (slightly wide eye distance, epicanthus, esotropia, mouth-opening appearance, short philtrum, and low-set ears). Gene detection results showed a de novo heterozygous frameshift mutation of the CHAMP1 gene at the chromosomal location of chr13:115089847, and nuclear acid was changed to c.530delCinsTTT, resulting in a change in amino acid to p.S177Ffs*2. Therefore, the boy was diagnosed with autosomal dominant intellectual disability-40 caused by the mutation in the CHAMP1 gene. This case report suggests that for children with unexplained intellectual disability, especially those with generalized hypotonia and severe language disorder, the possibility of CHAMP1 gene mutation should be considered, and genetic testing should be performed as early as possible.

[Effect of suspension exercise training on motor and balance functions in children with spastic cerebral palsy].

OBJECTIVE: To study the effect of suspension exercise training on motor and balance functions in children with spastic cerebral palsy. METHODS: A total of 97 children with spastic cerebral palsy were randomly divided into an observation group with 49 children and a control group with 48 children. Both groups were given routine rehabilitation training, and the children in the observation group were given suspension exercise training in addition. The scores of the D and E domains of the 88-item version of the Gross Motor Function Measure (GMFM-88) and Berg Balance Scale (BBS) were recorded before treatment and at 1, 3, and 6 months after treatment. Surface electromyography was performed to observe the changes in the root mean square (RMS) of surface electromyogram signals of the adductor muscle and the gastrocnemius muscle. RESULTS: Over the time of treatment, both groups had varying degrees of improvement in the scores of the D and E domains of GMFM-88 and BBS. Compared with the control group, the observation group had significantly greater improvements in D and E functional areas and balance function (P<0.05). Both groups had reductions in the RMS of the surface electromyogram signals of the adductor muscle and the gastrocnemius muscle over the time of treatment, and the observation group had significantly greater reductions than the control group (P<0.05). CONCLUSIONS: Suspension exercise training can effectively improve the motor and balance functions of children with spastic cerebral palsy.

[Prospective study of ketogenic diet in treatment of children with global developmental delay].

OBJECTIVE: To study the effect of ketogenic diet (KD) on neurobehavioral development, emotional and social behaviors, and life ability in children with global developmental delay (GDD). METHODS: A prospective case-control study was performed for hospitalized children with GDD, who were randomly divided into KD treatment group (n=40) and conventional treatment group (n=37). The children in both groups were given comprehensive rehabilitation training, and those in the KD treatment group were given modified Atkins diet in addition to the comprehensive rehabilitation training. The children in both groups were assessed with the Gesell Developmental Scale, Chinese version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Child Behavior Checklist (CBCL), and Infants-Junior High School Students' Social Life Abilities Scale (S-M scale) before treatment and after 3, 6, and 9 months of treatment. The two groups were compared in terms of the improvements in neurobehavioral development, emotional and social behaviors, and social life ability. RESULTS: After 3, 6, and 9 months of treatment, the KD treatment group had significantly greater improvements in the scores of the adaptive, fine motor, and language quotients of the Gesell Developmental Scale compared with the conventional treatment group (P<0.05); the KD treatment group had significantly greater improvements in CITSEA/CBCL scores than the conventional treatment group (P<0.05). The KD treatment group had a greater improvement in the score of the S-M scale after 9 months of treatment (P<0.05). During the KD treatment, 6 children experienced diarrhea and 1 experienced mild urinary stones. CONCLUSIONS: KD can improve the neurobehavioral development and behavioral and emotional behaviors in children with GDD, and it has few adverse effects.

[Effect of botulinum toxin A injection in the treatment of gastrocnemius spasticity in children aged 9-36 months with cerebral palsy: a prospective study].

OBJECTIVE: To investigate the long-term clinical efficacy and adverse effects of botulinum toxin-A (BTX-A) injection in the treatment of gastrocnemius spasticity in children aged 9-36 months with cerebral palsy. METHODS: Eighty children aged 9-36 months with cerebral palsy and gastrocnemius spasticity were selected and randomly divided into a BTX-A injection group and a conventional treatment group (n=40 each). The children in the BTX-A injection group received injections of BTX-A guided by color Doppler ultrasound and 4 courses of rehabilitation training after injection. Those in the conventional treatment group received 4 courses of the same rehabilitation training alone. Before treatment and at 1, 2, 3, and 6 months after treatment, the modified Tardieu scale (MTS) was applied to assess the degree of gastrocnemius spasticity, the values in the passive state measured by surface electromyography (sEMG) were applied to evaluate muscle tension, and the Gross Motor Function Measure (GMFM) was used to evaluate gross motor function. RESULTS: Compared with the conventional treatment group, the BTX-A injection group had significantly greater reductions in MTS score and the values in the passive state measured by sEMG (P<0.05), as well as significantly greater increases in joint angles R1 and R2 in MTS and gross motor score in GMFM (P<0.05). No serious adverse reactions related to BTX-A injection were found. CONCLUSIONS: BTX-A injection is effective and safe in the treatment of gastrocnemius spasticity in children aged 9-36 months with cerebral palsy.

Acupuncture reduced apoptosis and up-regulated BDNF and GDNF expression in hippocampus following hypoxia-ischemia in neonatal rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Acupuncture attenuates neuronal damages following ischemia. AIM OF THE STUDY: The purpose of the present study was to investigate the beneficial effects of acupuncture on hypoxia-ischemia induced brain damages in neonatal rats. MATERIALS AND METHODS: Male postnatal 7 days rats were randomly divided into 3 groups: sham control (sham), hypoxia-ischemia (HI), and HI plus acupuncture treatment (HI+Acu). The rats in HI and HI+Acu groups were submitted to model of neonatal HI, established by occluding the left common carotid artery followed by a 3.5h period of hypoxia (8% O2-92% N2). At 24h after HI, animals were stimulated by acupuncture treatment once a day and the treatment continued during 4 weeks, 5days/week. Behavioral functions, learning and memory ability, and body weight were observed at different time-points after HI. DNA fragmentation assay were performed with TUNEL staining to evaluate apoptosis and expression levels of mitochondrial Bcl-2, mitochondrial Bax, Cleaved caspase 3, Cleaved caspase 9 in the damaged hippocampus were detected by western blotting 28 days following HI. GDNF, BDNF levels in hippocampus were also determined. RESULTS: The results showed that acupuncture significantly promoted growth and development, improved neurobehavioral function, learning and memory ability after 20 days' treatment. Furthermore, we obtained one interesting finding that acupuncture attenuated cellular apoptosis and up-regulated GDNF and BDNF levels in hippocampus. CONCLUSIONS: All of these results suggest that acupuncture as a potential treatment may exert neuroprotective effects via inhibiting cellular apoptosis, increased GDNF and BDNF expression levels in rat hippocampus experiencing HI.

MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy.

MicroRNA-9 (miR-9) has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3)-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9(+) group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

[Therapeutic effects of different doses of botulinum toxin A injection on tiptoe deformation in children with cerebral palsy].

OBJECTIVE: To study the therapeutic effects of different doses of botulinum toxin A (BTX-A) injection on tiptoe deformation in children with cerebral palsy. METHODS: A total of 256 children with tiptoe deformation due to spastic cerebral palsy were classified into group A (muscle tension levels I-II, n=147) and group B (muscle tension levels III-IV, n=109). Group A was randomly divided into group A1 (injected with high-dose BTX-A, n=73) and group A2 (injected with low-dose BTX-A, n=74). Group B was randomly divided into group B1 (injected with high-dose BTX-A, n=55) and group B2 ( injected with low-dose BTX-A, n=54). The dose of BTX-A was 6 U/kg for groups A1 and B1 and was 3 U/kg for groups A2 and B2. Before the injection and at 1,2,6, and 12 months after injection, the muscle tension of limbs was evaluated with the modified Ashworth Scale, and the recovery of motor function of lower limbs was assessed with the Gross Motor Function Measure (GMFM). RESULTS: Before and after treatment, there were no significant differences in Ashworth and GMFM scores between groups A1 and A2 (P>0.05). After treatment, group B1 had a significantly reduced Ashworth score and a significantly increased GMFM score, and group B1 had a significantly lower Ashworth score and a significantly higher GMFM score compared with group B2 (P<0.05). For groups A and B, Ashworth score gradually declined post-treatment, reached the lowest point at 3 months after treatment, and returned to the level before treatment at 12 months after treatment; GMFM score gradually increased post-treatment and reached the peak level at 12 months after treatment (P<0.05). CONCLUSIONS: The level of muscle tension should be considered when BTX-A injection is used for treating tiptoe deformation in children with cerebral palsy. It makes no difference to use high- or low-dose BTX-A when the muscle tension level is within I-II, but high-dose BTX-A has a better performance in reducing muscle tension and improving motor function when the muscle tension level is within III-IV.

[Therapeutic effect of ketogenic diet for refractory epilepsy in children: a prospective observational study].

OBJECTIVE: To study the clinical efficiency, electroencephalogram (EEG) changes and cognitive improvements of ketogenic diet (KD) in children with refractory epilepsy. METHODS: Twenty pediatric patients (7-61 months in age) with refractory epilepsy were recruited between August 2012 and August 2013. KD therapy was performed on all participants for at least 3 months based on a fasting initiation protocol with the lipid-to-nonlipid ratio being gradually increased to 4 : 1. Seizure frequency, type and degree were recorded before and during KD therapy. A 24 hours video-electroencephalogram (V-EEG) examination and Gesell Developmental Scale assessment were performed prior to KD therapy, and 3, 6, 9 months after KD therapy. RESULTS: Six patients became seizure free after KD therapy, with a complete control rate of 30%. Seizure frequency reduction occurred in 13 (65%) patients, EEG improvement in 8 (40%) patients, and improvement in Gesell Developmental Scales (gross motor and adaptability in particular) in 6 (30%) patients. The KD therapy-related side effects were mild. CONCLUSIONS: KD therapy is safety and effective in reducing seizure frequency and improving EEG and cognitive function in children with refractory epilepsy.

[Clinical analysis of 322 cases of non-epileptic cerebral palsy].

OBJECTIVE: To study the clinical features of non-epileptic seizures associated with cerebral palsy (CP) in children. METHODS: A total of 1 198 children with CP (age: 9 months to 6 years) were enrolled. The children with paroxysmal events were monitored by 24 hrs video-EEG (VEEG) to make sure the seizures were epileptic or non-epileptic. The symptoms, age, CP types and EEG features were observed in children with non-epileptic CP. RESULTS: Five hundred and seventy-eight children (48.24%) presented paroxysmal events. The seizures were epileptic in 231 children (19.28%) and non-epileptic in 322 cases (26.88%). In the 322 cases of non-epileptic CP, the paroxysmal events were of various kinds, including non-epileptic seizure tonic, seizure shake head, shrug shoulder or head hypsokinesis, cry or scream, panic attacks, sleep myoclonic and stereotyped movement. One hundred and fifty-eight (49.1%) out of the 322 children demonstrated nonspecific EEG abnormalities. One hundred and eleven children (34.5%) were misdiagnosed as epilepsy in primary hospitals. The CP children less than one year old showed higher frequency of non-epileptic seizures than the age groups over 1 year and 3 to 6 years. The frequency of non-epileptic seizures was the highest in children with spastic CP (168 cases, 52.2%), followed by dyskinetic CP (69 cases, 21.4%) and mixed type CP (65 cases, 20.2%). CONCLUSIONS: The paroxysmal events in children with CP partially are non-epileptic seizures and it is important to differentiate non-epileptic from epileptic seizures. The frequencies of non-epileptic seizures may be associated with a child's age and CP type.