[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.

[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.

[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.

Mutation of acceptor splice site of the SEDL gene in X-linked spondyloepiphyseal dysplasia tarda causes the activation of cryptic splice site.

OBJECTIVE: To further investigate the genetic basis of hereditary X-linked spondyloepiphyseal dysplasia tarda (SEDL) and provide useful information for the prevention and treatment of the disease. METHODS: RT-PCR and cDNA sequencing were used to test mRNA expression of SEDL gene in a patient with 13 bp deletion of SEDL gene involving the acceptor splice site of intron 5. RESULTS: Of two different sizes of mRNA products identified in the patient, the 393 bp product was created due to the activation of cryptic splice site within exon 6; the 433 bp product was completely consistent with the part of genomic sequence on chromosome 8. CONCLUSION: The intragenic deletion that occurred in the acceptor splice site of the 3'region of intron 5 and the 5' coding region of exon 6 results in the activation of a cryptic splice site within exon 6, which causes 47 bp deletion of the resulting mRNA followed by a frameshift that would add two missense amino acids and then be followed by a termination codon (D109-S123del; S124fsX126). In addition, the mutation may activate the transcription of pseudogene SEDLP2 on chromosome 8 to partly complement the function of SEDL protein.

[Association analysis on the polymorphisms of PCOL2 and Sp1 binding sites of COL1A1 gene and the congenital dislocation of the hip in Chinese population].

OBJECTIVE: To investigate the polymorphism distribution of the PCOL2 and Sp1 binding sites of the collagen type I alpha 1(COL1A1) gene in Chinese population and explore their relationship with congenital dislocation of the hip (CDH). METHODS: The PCOL2 polymorphism (-1997 G/T) in COL1A1 promoter and the Sp1 polymorphism (1546 G/T) in intron 1 were genotyped in 243 members from 81 CDH nuclear family trios by the technique of polymerase chain reaction-restriction fragment length polymorphism, and then transmission disequilibrium test was used to analyze the data of genotypes. RESULTS: No statistically significant association was observed between CDH and PCOL2 polymorphism. Significant differences of genotype and allele frequency distributions were detected between the Chinese population and the Caucasian population in Spain, and between the Chinese population and the Caucasian population in America. The allele at the Sp1 site that has been found to be polymorphic in other populations was not found in Chinese. CONCLUSION: There exists racial difference in the distribution of the PCOL2 and Sp1 polymorphisms of COL1A1 gene. The results suggest that the PCOL2 and Sp1 polymorphisms may not be the major susceptibility gene of CDH in Chinese population.

[Glial fibrillary acidic protein mutation in a Chinese girl with infantile Alexander disease].

OBJECTIVE: To investigate the molecular basis of infantile Alexander disease in a Chinese patient, which may yield useful information for further genetic counseling. METHODS: DNA sequencing analysis and restriction endonuclease analysis were used to detect the mutation of glial fibrillary acidic protein (GFAP) gene in a patient with clinically diagnosed Alexander disease, in her parents and in 50 healthy controls. RESULTS: A 249C>T (R79C) mutation was identified in the exon 1 of the GFAP gene but not in her parents and the controls. CONCLUSION: The study on mutation of GFAP gene in Chinese patients with Alexander disease has never been reported previously. The mutation analysis of GFAP gene can provide valuable information for the diagnosis of Alexander disease and can serve as a reliable method of prenatal diagnosis for the family.

[Identification of a novel mutation of the SEDL gene in X-linked spondyloepiphyseal dysplasia tarda].

OBJECTIVE: To investigate further the genetic basis of hereditary X-linked spondyloepiphyseal dysplasia tarda (SEDL). METHODS: Single strand conformation polymorphism (SSCP) combined with polymerase chain reaction and denaturing polyacrylamide gel electrophoresis were used to detect the mutation for the coding exons of SEDL gene as well as their exon/intron boundaries in 5 unrelated Chinese boys clinically diagnosed as having SEDL. DNA sequencing analysis was further used to identify the mutation. RESULTS: The 13 bp deletion mutation consisting of IVS5-2-1delAG and 322-332del TTTTCAATGAA was identified in one of SEDL patients, but not detected in 30 chromosomes from 30 unrelated normal male individuals. CONCLUSION: This is a novel mutation cosegregated with the patient's skeletal disease. The intragenic deletion occurred in the acceptor splice site of the 3' region of intron 5 and the 5' coding region of exon 6, which may result in one or a combination of splicing defects. The results of this study expand the spectrum of SEDL mutations associated with SEDL, and this will help to elucidate further the role of this novel protein in the etiology of this form of osteochondrodysplasia.