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Objective:To describe the clinical features of pediatric biotinase deficiency (BTD) manifested as spinal cord disease.Methods:The clinical data of a child with spinal cord lesions due to biotinase deficiency, diagnosed in Beijing Children′s Hospital in 2020, were collected. The cases with complete clinical data retrieved on literature reported in China National Knowledge Infrastructure, Wanfang Data knowledge Service Platform and PubMed (up to August 2021) by using search terms of biotinase deficiency, pediatric, spinal cord, myelopathy and myelitis were summarized.Results:The patient was a 3 years and 5 months old boy with the main clinical manifestations of subacute progressive limb weakness and wheezing. Physical examination showed sparse hair, rough skin, spastic paraparesis and developmental delay. Cerebrospinal lactic acid was increased (5.67 mmol/L). Cranial magnetic resonance imaging (MRI) showed diffuse T 2/fluid attenuated inversion recovery hyperintensity of the midbrain, dorsal pons, edulla, periacqueductal grey and optic tracts. Spinal cord lesions were extended from the medulla up to the level of the conus. Urineketone bodies and 3-hydroxyisurate were increased. The activity of biotinidase was 0.27 pmol/min (3 mm disc), being 7% of mean normal serum activity. Genetic studies revealed homozygous mutation in the BTD gene [c.284T>A (p.I95N)]. After biotin supplementation for 6 months, the only evident abnormality was residual spasticity of lower limbs. Fourteen English literatures and 2 Chinese literatures including 18 cases were collected. The onset age was from 2 months to 15 years (median age was 4 years). Among them, 11 cases had cranial MRI abnormalities, of which all involved brain stem, 6 cases involved optic tracts and (or) optic chiasm. All 18 cases had spinal cord MRI abnormalities with longitudinally extensive lesion, mostly involved cervical and thoracic spinal segments, and 3 cases involved all spinal segments. Twelve cases received immunotherapy, and 6 were partially improved, 6 were completely invalid. After biotin supplementation, 12 patients had neurological disability. Conclusions:BTD should be included in the differential diagnosis of subacute myelopathy, regardless of the onset age. Early diagnosis and treatment can prevent irreversible neurological damage.
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Objective:To investigate the clinical and laboratory characteristics of subacute sclerosing panencephalitis (SSPE).Methods:The clinical, laboratory and electroencephalogram (EEG) data of eight patients with SSPE who admitted to the Department of Neurology, Beijing Children's Hospital, Capital Medical University, from May 2014 to February 2019 were retrospectively analyzed and followed up.Results:Four of the patients were male and four were female, who aged from two years and seven months to 13 years and five months with a median onset age of five years and six months. All of the eight cases had disease onset with progressive mental and physical regression, then developed periodic myoclonic seizures at the course of 11 days to 11 months. Video EEG examinations showed persistent generalized periodic complex waves with long interval (3-20 s). The IgG titers of measles virus in blood and cerebrospinal fluid of all cases were significantly increased. There was no significant abnormality in blood/urine metabolism screening nor head magnetic resonance imaging for the first time. Five cases performed head magnetic resonance imaging again, in which two cases with deepening hemispheric sulcus, two cases with cerebral white matter signal abnormalities. Antiepileptic drugs, gamma globulin, adrenocortical hormone and antiviral drugs were used after diagnosis though all were ineffective. All patients presented progressive deterioration. During the follow-up period of three months to two years and seven months, four patients died, of which three patients died at the time of five months, one year and two months, two years and six months after onset respectively, and the other one was unknown.Conclusions:The diagnostic clues of SSPE are progressive mental and physical regression, recurrent myoclonic seizures during period Ⅱ, as well as the extensive periodic complex waves of EEG. It is necessary to detect measles virus IgG antibody in blood and cerebrospinal fluid to make a definite diagnosis. There is no specific treatment for SSPE and its prognosis is very poor.
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Objective@#To describe the clinical manifestations of central nerve system inflammatory demyelinating disease associated with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IDD) in children, and to explore the clinical characteristics of the children.@*Methods@#The clinical and laboratory characteristics of the patients diagnosed in Beijing Children′s Hospital, Capital Medical University, from October 2016 to August 2018 were described, and the clinical data of the patients with unipolar and recurrent diseases were compared.@*Results@#A total of 50 patients were included, among whom the ratio of male to female was 24:26, and the average age of onset was (6.7±3.1) years old (0.4-12.6 years old). There was no significant difference in the age of onset between boys and girls(t=0.712, P=0.480). The main symptoms included fever (31/50 cases), encephalopathy (26/50 cases) and optic neuritis (22/50 cases), etc.In the last follow-up, 26 patients (52.0%) had a monophasic course and 24 patients (48.0%) had a recurrent course.There were age differences in encephalopathy and ataxia in the first episode of [(5.7±2.8) years old vs.(8.1±3.0) years old, (5.0±2.5) years old vs. (7.7±3.0) years old](t=2.746, P=0.009; t=2.837, P=0.007). The average number of recurrence was (2.1±1.4) times (1-7 times), in which 17 cases (70.8%) of recurrence presented within 12 months and 20 cases (83.3%) of recurrence presented within 24 months after onset.Convulsion incidences of recurrent cases were 10 cases and 13 cases respectively in the first episode and recurrent courses, which were significantly higher than those of monophasic cases (4 cases, 4 cases)(χ2=7.912, P=0.005; χ2=8.365, P=0.004). All patients were sensitive to first-line immunotherapy.Seven patients with recu-rrence were treated with mycophenolatemofetil, and 17 patients with repeated first-line therapy.In the last follow-up, all patients were in remission and 2 patients had mild neurological dysfunction.@*Conclusions@#MOG-IDD can occur in childhood.Encephalopathy and optic neuritis are the most common symptoms.Encephalopathy and ataxia are more common in young children.Convulsions may indicate the course of recurrence.
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Objective To study the effect of repetitive normobaric hypoxic preconditioning (RNHP) on white matter lesions (WMLs) and cognitive impairment in chronic cerebral ischemia rats.Methods Twenty-four healthy adult male SD rats were divided into sham operation group,model group,and RNHP group (8 in each group).The bilateral common carotid arteries in sham operation group were isolated but not ligated in ambient air,those in model group were ligated in ambient air,and those in RNHP group were preconditioned for 2 weeks before ligation.Their cognitive function was assessed in Morris water maze test,their WMLs were caluculated with KlüverBarrera staining.The astroglia,microglia and oligodendrocyte in cerebral white matter were stained with immunolabelling technique using antibodies to glial fibrillary acidic protein,Iba-1 and CNPase.Results The percentage of target quadrant swimming time was significantly higher in RNHP group and sham operation group than in model group (27.26％ ± 2.06％,29.06％ ± 1.72％ vs 20.58％±2.23％,P＜0.05,P＜0.01).The scores of WMLs in corpus callosum,caudate putamen and anterior commissure were significantly lower,the number of astrocytes and microglias was significantly smaller while that of oligodendrocytes was significantly greater in RNHP group and sham operation group than in model group (P＜0.05,P＜0.01).Conclusion RNHP can improve WMLs and cognitive impairment in chronic cerebral ischemia rats.
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Objective@#To analyze the clinical and genetic features of progressive cavitating leukoencephalopathy (PCL).@*Method@#The data of clinical and genetic features of 4 PCL patients diagnosed by Beijing Children′s Hospital between January 2015 and January 2016 were analyzed. The cases with complete clinical data retrieved on literature search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to August 2016) by using search terms of"NDUFV1" ,"NDUFS1" , or"leukoencephalopathy" , were summarized.@*Result@#There were three females and one male, two of which were compatriots. The age of onset ranged from 6 months to 15 months. All four children′s first symptoms were motor development regression, and the developmental milestones were almost normal before the onset. Of the 4 patients, 3 had cognitive impairment, 1 had seizures, 4 had dystonia and pyramidal impairment, 2 had emaciation, and 1 had nystagmus. The lactate concentrations of 4 patients were normal in blood. One patient had lactaciduria in the urinary organic acid analysis. Cranial magnetic resonance imaging (MRI) of all patients showed leukoencephalopathy, involved in the corpus callosum, and three patients accompanied by cystic lesions. Follow up for 2-13 years showed that the physical and language development were improved. Genetic analysis revealed that mutations in NDUFS1 were found in three patients and NDUFV1 mutation was found in one patient. All six mutations (p.Arg377Cys and p. Arg377His in NDUFV1; p. Arg482Glyfs*5, p.Thr368Pro, p.Tyr454X and p. Asp565Gly in NDUFS1) are novel. Five English case reports including 10 PCL patients were collected. Together with this group of 4 cases, a total of 14 cases were involved. All 14 children patients had motor development regression, 11 cases had cognitive impairment and dystonia, 6 cases had pyramidal impairment, 5 cases had irritability, 4 cases had epilepsy and nystagmus, 3 cases had strabismus and swallowing difficulty. Cranial MRI showed patchy leukoencephalopathy with cavities, involved in the corpus callosum. Follow up for 19 months-15 years that the neurology development were improved slowly in all patients.@*Conclusion@#NDUFS1 and NDUFV1 gene mutation screening should be performed firstly in patients with PCL clinical and imaging feature.
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Objective To investigate the changes of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP)in acute phase of cerebral infarction. Methods From March 2011 to June 2012,95 patients with early cerebral infarction from the Neurology Clinic,the Emergency Department and the Cerebral Apoplexy Screening Project Base,and the Neurology Ward of Renhe Hospital were used as an infarction group;61 non-stroke subjects received physical examination in the Physical Examination Center of our hospital in the same period were used as a control group. The cerebral infarction group and the patients with cerebral infarction in different onset of time groups (an onset 0. 05). The analysis results of ROC curve of UCH-L1 and GFAP for diagnosis of acute cerebral infarction showed that when the plasma UCH-L1 was ≥0. 18 μg/ L,the sensitivity and specificity of UCH-L1 were 68% and 74%respectively;When the plasma GFAP was ≥0. 11 μg/ L,the sensitivity and specificity of GFAP were 70% and 86% respectively. The area under the ROC curve of UCH-L1 and GFAP diagnosis of cerebral infarction were 0. 64 and 0. 71 respectively. Conclusions UCH-L1 and GFAP have obvious change in acute phase of cerebral infarction. UCH-L1 and GFAP may have certain correlation with the severity of stroke.
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<p><b>OBJECTIVE</b>To investigate the clinical and genetic features of a Chinese girl with Schwartz-Jampel syndrome (SJS).</p><p><b>METHOD</b>To analyze the clinical and genetic data of a girl with Schwartz-Jampel syndrome who was sent to neurology outpatient department of Beijing Children's Hospital in Auguest of 2010. Reports on Schwartz-Jampel syndrome published until July of 2015 were searched and the clinical and genetic characteristics of reported cases were summarized.</p><p><b>RESULT</b>At 8 months after birth, the girl showed myotonia; at 1 year old when she was walking alone she had myotonia of lower limbs, both feet evaginated, walked slowly and was prone to fall. At 2 years of age, she could not climb up stairs, at 3 years she could not jump continuously. At 3 years and 7 months of age when the girl was taken to neurology outpatient department, on examination, she had a dull facial expression, rigid lips and could not fully open her mouth, a micromandible, low-set and prominent ears, systemic muscle rigidity, there were muscular nodes formation on the limbs and gait stiffness. She had high level of creatine kinase and atlanto-axial joint subluxation on cervical CT reconstruction. She also had spontaneous myotonia-like discharges on needle electromyography (NEMG). X-ray of limbs showed metaphyseal dysplasia. The patient was treated with neurologic rehabilitation and carbamazepine. The myotonia at the last follow-up at her 8 years of age was the same as at the onset. On her HSPG2 gene, two novel heterozygous mutations c.10776delT on exon 78 and c.5702-5G>A on intron 45 were found. c.10776delT resulted in the amino acid change on p.Ala3592fsX6 and c.5702-5G>A maybe changed protein splicing. No reports were found among Chinese journals, while 7 reports were found in English literature. The total 34 mutations were known in reviewed reports, which included eleven deletion or insertion, twelve splice site, eight missense, and three nonsense mutations. Four patients had a single mutation. No definite genotype-phenotype correlation was identified.</p><p><b>CONCLUSION</b>Schwartz-Jampel syndrome is a rare autosomal-recessive hereditary disease appears to be slowly progressive, in which distinctive clinical features were induced by HSPG2 gene mutation. We reported the c.10776delT on exon 78 and c.5702-5G>A on intron 45 which were not reported previously. This is the first report of Schwartz-Jampel syndrome of which genetic mutations was identified in a Chinese child.</p>
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Child , Child, Preschool , Female , Humans , Infant , Asian People , Carbamazepine , Therapeutic Uses , Exons , Heterozygote , Introns , Mutation , Osteochondrodysplasias , Diagnosis , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical and PMM2 gene mutation features of congenital disturbance of glycosylation caused by PMM2 gene mutation (PMM2-CDG, previously known as CDG 1a).</p><p><b>METHOD</b>The clinical data of two Chinese patients who were clinically diagnosed as PMM2-CDG at neurology department of Beijing Children's Hospital in 2012 were retrospectively collected. The gene mutations were identified by Sanger sequencing.</p><p><b>RESULT</b>Both patients were female, aged 1 year and 1 month and 8 months respectively. The main clinical features of the two cases were developmental delay after birth, chronic diarrhea and metabolic acidosis, associated with elevated serum transaminases, and decreased antithrombin III activity. Physical examination showed esotropia, inverted nipples, and abnormal subcutaneous fat pads. The cranial MRI showed cerebellar atrophy. Both cases were treated with occupational therapy, physical therapy and speech therapy. The development was gradually improved but also delayed as compared with normal peers during follow-up for more than 3 years. Genetic analysis showed that patient 1 was compound heterozygous for c. 422G>A(p.Arg141His), which was reported for known pathogenic mutation, and c. 669C>A(p.Asp223Glu), was a new mutation. The patient 2 showed compound heterozygous mutation for c. 634A>G (p.Met212Val)and c. 713G>C(p.Arg238Pro), which were both new mutations.</p><p><b>CONCLUSION</b>PMM2-CDG is a rare metabolic disease, and the diagnosis should be considered in a child with developmental delay, elevated serum transaminases, decreased antithrombin III activity, inverted nipples, abnormal subcutaneous fat pads, esotropia, and cerebellar atrophy on MRI. It can be confirmed by PMM2 gene analysis.</p>
Subject(s)
Female , Humans , Infant , Asian People , Congenital Disorders of Glycosylation , Genetics , DNA Mutational Analysis , Developmental Disabilities , Genetic Testing , Glycosylation , Heterozygote , Magnetic Resonance Imaging , Mutation , Phosphotransferases (Phosphomutases) , Genetics , Retrospective StudiesABSTRACT
Remote ischemic postconditioning can induce cerebral ischemic tolerance and have neuroprotective effects.It has provided a novel strategy for the treatment of ischemic cerebrovascular disease.In recent years,the mechanism research of remote ischemic postconditioning and clinical applications have made significant progress and have shown encouraging prospects of clinical transformation.
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Objective To investigate the effect of acute irradiation by high power millimeter wave on the pathological changes of mouse lung tissue. Methods The BALB/c mice were vertically placed under the high power millimeter wave equipment with working frequency of 34. 1 GHz, and the mean output power were 5,10 and 12 W while the distance between the animal and the bottom of the irradiation horn were 10 mm and 20 mm, respectively. The mice were tied on the platform and continuously received irradiation until death. After immediate dissection, the mouse lung was quickly rinsed with 0.9% NaCl solution, fixed in 10% formaldehyde solution and mounted for paraffin section. After HE staining and image taken with a CCD camera, the Image Pro Plus software and quantitative image analysis by combining the mean optical density and area was used to determine the pathological injuries of the lung. Result Using the HA23. 16 and HA9. 92 pyramid horns with different physical parameter, the mice exposed to irradiation with high mean power of 12 W were dead most quickly, the death time was only about 110 s. Meanwhile, the death time was about 30 min after irradiation with the mean power of 5 W. There was significant hemorrhage in the mouse lung with high power millimeter irradiation, although the hemorrhage degree was different under different irradiation parameters. When the mean power were 10 and 12 W.the hemorrhage degree of lung was extremely high, where the bronchia and blood vessel of lung was markedly broken. A lot of cells of bronchia had been released. However, when the mean power was 5 W, the hemorrhage degree of lung was less observed, while the bronchia and blood vessels had not severe fracture. Conclusions High power millimeter wave wave irradiation has remarkable effect on mice lung. The damage degree of lung tissue is highly correlated with the mean power of millimeter wave irradiation. As the high power millimeter used in this study could result in significant thermal effect, the acute heat-induced response might lead to animal death by causing serious lung injury.