Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

Primary Study of Henan Cerebral Palsy Register and Rehabilitation Management System / 中国康复理论与实践

Objective:To introduce the construction of Henan Cerebral Palsy Register and Rehabilitation Management System (HCPRRMS) and to explore the construction project of regional register and surveillance of cerebral palsy. Methods:The construction process, registration content and preliminary results of HCPRRMS were systematically introduced. Results:HCPRRMS was independent developed in 2014. Since March, 2015, the system has been used to register information of patients with cerebral palsy in the Third Affiliated Hospital of Zhengzhou University. Until September, 2019, a total of 23 child rehabilitation institutions had used the registration management system. There were 1357 patients with cerebral palsy registered in this system, in which 936 cases (68.98%) were male, 501 cases (36.92%) were with gestational weeks < 37, 443 cases (32.65%) were with birth weight < 2500 g, and 430 cases (31.69%) were born with hypoxic-ischemic encephalopathy. Among them, the spastic cerebral palsy patients (1117 cases, 86.74%) accounted for the highest proportion. There was significant difference among types of cerebral palsy and the classification of GMFCS. A total of 1117 patients with cerebral palsy showed MRI-identified brain abnormalities, in which, periventricular leukomalacia accounted for the most (480 cases). For the complications, epilepsy accounted for 14.44% (196 cases), vision impairment accounted for 8.03% (109 cases), hearing impairment accounted for 11.64% (158 cases). Among 769 cases aged more than two years, language-speech dysfunction accounted for 52.66% (424 cases); and among 216 cases aged more than four years, mental retardation accounted for 37.96% (82 cases). Conclusion:HCPRRMS could help to understand the risk factors, clinical characteristics, and complications of cerebral palsy.

Therapeutic effects of different doses of botulinum toxin A injection on tiptoe deformation in children with cerebral palsy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the therapeutic effects of different doses of botulinum toxin A (BTX-A) injection on tiptoe deformation in children with cerebral palsy.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>