Research progress of nervous system damage in Pompe disease / 中国当代儿科杂志

Pompe disease, also known as glycogen storage disease type Ⅱ, is a rare autosomal recessive disease. With the application of enzyme replacement therapy, more and more patients with Pompe disease can survive to adulthood, and nervous system-related clinical manifestations gradually emerge. Nervous system involvement seriously affects the quality of life of patients with Pompe disease, and a systematic understanding of the clinical manifestations, imaging features and pathological changes of nervous system injury in Pompe disease is of great significance for the early identification and intervention of Pompe disease. This article reviews the research progress of neurological damage in Pompe disease.

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review / 中华儿科杂志

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

Immunization of category B vaccine and its influencing factors among children aged 0 to 6 in Hangzhou / 预防医学

Objective To explore the immunization of category B vaccine and its influencing factors among children aged 0 to 6 in Hangzhou City. Method We carried out an investigation with 685 parents of children aged 0 to 6 from January to February in 2017 by using stratified random sampling method. Statistical method was used to analyze the knowledge, behaviors and attitudes towards category B vaccine, and logistic regression was applied to explore the determinant factors of category B vaccine behavior. Results 670 parents were under actual survey, 467 children have been vaccinated at least one kind of category B, which accounts for 69.70％ and the rates of five main types of vaccine were lower than 30％. Logistic regression showed that people of citizen (OR=1.54, 95％ CI: 1.14-2.38) , able to distinguish category A or B vaccine (OR=2.05, 95％ CI: 1.26-3.33) , positive attitude towards category B vaccine (OR=2.46, 95％CI: 1.43-4.23), and higher affordable price (OR=3.15, 95％CI:2.07-4.80) were determinant factors of category B vaccine behavior . Conclusion The rate of category B vaccine behavior of children aged 0 to 6 is on a moderate level. The cognition and attitude of children' s parents on category A vaccine and category B vaccine have effect on the immunization status of category B vaccine among children aged 0 to 6 in Hangzhou.

A study on the immunization status of the left-behind children in the rural areas of Zhejiang Province / 预防医学

Objective To investigate the immunization status of the left-behind/non-left-behind children in the rural areas of Zhejiang Province. Methods Multi-stage cluster random sampling was adopted to recruit 0-6 years old children and their guardians in a rural mountainous county in Lishui District of Zhejiang Province. Household survey was conducted using structured questionnaires. Records of vaccination were obtained and verified in the local disease control and prevention center. Results A total of 420 questionnaires were issued, with a number of 416 were complete and valid. The Valid responsive rate was 99.05% . Among them, 97 were left-behind and 319 were non-left-behind children. The immunization coverage rates did not differ significantly between the left-behind and non-left-behind children. The timely immunization rates of the third shot of hepatitis B vaccine and the first shot of encephalitis vaccine differed significantly between left-and non left-behind children (P=0.049 and P=0.044, respectively) . Conclusion Immunization status of the left-behind children in the rural areas of Zhejiang province was in a good condition in general. The local disease control and prevention center should strengthen the communication, to promote immunization knowledge and to improve family supervision of the left-behind children.

Safety of intravenous thrombolysis in cerebral microbleeds patients with prior antiplatelet therapy / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the safety of intravenous thrombolysis (IVT) in cerebral microbleeds (CMBs) patients with prior antiplatelet therapy.</p><p><b>METHODS</b>Four hundred and forty nine patients with acute ischemic stroke aged (66.8 ± 12.9) years, including 298 males and 151 females, underwent susceptibility-weighted imaging (SWI) examination and MRI-guided IVT therapy between June 2009 and June 2015. The presence of CMBs, previous antiplatelet therapy, HT subtypes according to ECASS II criteria and functional outcome based on modified Rankin scale (mRS) at 3 months were analyzed in logistic regression model.</p><p><b>RESULTS</b>Total 934 CMBs were detected in 172 (38.3%) patients, among whom 63 (14.0%) previously received antiplatelet therapy. All patients received intravenous recombinant tissue-plasminogen activator (rt-PA) for thrombolysis with the onset-to needle time of (229.0 ± 103.7) min. The pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 10 (IQR 5-15). Logistic regression analysis indicated that prior antiplatelet use increased neither risk of parenchymal hematoma (PH) (OR=0.809,95% CI:0.201-3.262, P=0.766) nor adverse functional outcome (OR=1.517, 95% CI:0.504-4.568, P=0.459) in patients with CMBs; while in patients with multiple CMBs (≥ 3) prior antiplatelet use increased risk of hemorrhagic transformation (OR=9.737, 95% CI: 1.364-69.494, P=0.023), but not adverse functional outcome (OR=1.697, 95% CI:0.275-10.487, P=0.569).</p><p><b>CONCLUSION</b>The study indicates that in patients with CMBs, thrombolytic therapy should not be excluded due to the prior use of antiplatelet; however, the larger prospective studies are needed in future for patients with multiple CMBs.</p>

Cerebral lesions of DWI hyperintensity in patients with subacute stroke assessed by intravoxel incoherent motion technique / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the cerebral lesions of diffusion weighted imaging (DWI) hyperintensity in patients with subacute stroke with intravoxel incoherent motion (IVIM) technique.</p><p><b>METHODS</b>The clinical data of 20 patients with ischemic stroke (3 to 7 d after onset) who underwent DWI and IVIM scanning between June 2014 and July 2015, were retrospectively analyzed. The parameters from IVIM including slow diffusion coefficient (D), fast diffusion coefficient (D(*)) and perfusion fraction (f) were processed. DWI hyperintensity was segmented by its signal intensity greater than the mean+2 standard deviations of the value in the homologous contralateral region. Then, DWI hyperintensity was classified into two regions of interest (ROIs): infarction core and peri-core with the ADC threshold of 0.55 × 10⁻³ mm²/s. The mirrored ROIs of infarction core and peri-core were also obtained. Then, we measured the values of ADC and D, D(*) and f in these ROIs. The ratios of ADC (rADC), D (rD), D(*) (rD(*)) and f (rf) were also calculated (e.g., rADC=ADCinfarction core/ADCmirrored region).</p><p><b>RESULTS</b>Compared with mirrored region, ADC, D and f in the infarction core region decreased by 45% (P<0.001), 42% (P<0.001) and 32% (P<0.001), respectively; while ADC, D and f in the peri-core region decreased by 22% (P<0.001), 32% (P<0.001) and 8% (P=0.009), respectively. The values of rADC, rD, rD(*) and rf in the infarction core region were significantly lower than those in the peri-core region (all P<0.001). Pearson analysis showed that rADC was positively correlated with rf in the peri-core region (r=0.467, P=0.038).</p><p><b>CONCLUSION</b>During subacute stage of stroke, compared to the infarction core region within DWI hyperintensity, D and f increase in the peri-core region of DWI hyperintensity, reflecting the increased water diffusion in microstructure and perfusion volume in microvasculature. This result shows that the potential reason for the heterogeneous ADC signal is associated with the disappearance of cellular edema and microvascular compensatory with increased blood volume.</p>