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Objective: To summarize the phenotypes of epilepsy in patients with MBD5 gene variants. Methods: A total of 9 epileptic patients, who were treated in the Department of Pediatrics, Peking University First Hospital from July 2016 to September 2021 and detected with MBD5 gene pathogenic variants, were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively. Results: Among 9 patients, 6 were male and 3 were female. Age at seizure onset ranged from 5 to 89 months. Multiple seizure types were observed, including generalized tonic clonic seizures (GTCS) in 7 patients, myoclonic seizures in 5 patients, focal seizures in 5 patients, atypical absence seizures in 3 patients, atonic seizures in 2 patients, myoclonus absence seizures in 1 patient, epileptic spasms in 1 patient, and tonic seizures in 1 patient. There were 8 patients with multiple seizure types, 2 patients with sensitivity to fever and 5 patients with clustering of seizures. Two patients had a history of status epilepticus. All patients had developmental delay before seizure onset. Nine patients had obvious language delay, and 6 patients had autism-like manifestations. Five patients had slow background activity in EEG. Interictal EEG showed abnormal discharges in 9 patients. Brain magnetic resonance imaging (MRI) was normal in all patients. A total of 9 epileptic patients carried MBD5 gene variants, all of them were de novo variants. There were MBD5 gene overall heterozygous deletion in 1 patient, large fragment deletions including MBD5 gene in 3 patients and single nucleotide variations (c.300C>A/p.C100X, c.1775delA/p.N592Tfs*29, c.1759C>T/p.Q587X, c.150_151del/p.Lys51Asnfs*6, c.113+1G>C) in 5 patients. The age at last follow-up ranged from 2 years and 9 months to 11 years and 11 months. At the last follow-up, 2 patients were seizure-free for more than 11 months to 4 years 6 months, 7 patients still had seizures. Conclusions: The initial seizure onset in patients with MBD5 gene variants usually occurs in infancy. Most patients have multiple seizure types. The seizures may be fever sensitive and clustered. Developmental delays, language impairments, and autistic behaviors are common. MBD5 gene variants include single nucleotide variations and fragment deletions. Epilepsy associated with MBD5 gene variants is usually refractory.
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , DNA-Binding Proteins/genetics , Electroencephalography , Epilepsies, Myoclonic/genetics , Epilepsy/genetics , Fever , Nucleotides , Phenotype , Retrospective Studies , Seizures/geneticsABSTRACT
Objective: To compare the effect of galectin-3 (Gal-3), NT-proBNP and echocardiography paramerters on assessing cardiac function in patients with chronic heart failure (HF). Methods: A total of 144 patients treated in our hospital from 2016-03 to 2016-11 were enrolled. According to the NYHA classification, the patients were divided into 2 groups: HF group and Normal cardiac function group. n=72 in each group. Basic clinical information was collected, blood levels of Gal-3 and NT-proBNP were examined, echocardiography was conducted to measure left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD). Correlations between Gal-3, NT-proBNP and echocardiography parameters were studied, the abilities of Gal-3, NT-proBNP and echocardiography for estimating HF were compared. Results: Compared with Normal cardiac function group, HF group had increased blood levels of NT-proBNP [3499.5 (1431.3-9088.0) ng/L] vs [384.1 (122.1-1540.5) ng/L] and Gal-3 [3.0 (1.71-5.8) pg/ml] vs [1.9 (1.4-2.6) pg/ml], decreased LVEF [49.5% (42%-58%)] vs [62.5% (59%-67%)], enlarged LVEDD [52.0 (46.3-57.8) mm] vs [46.0 (42.0-49.0) mm] and elevated serum creatinine [113.6 (90.5-152.7) umol/L] vs 82.4 (69.1-97.4) umol/L], all P<0.05. Correlation analysis showed that NT-proBNP and Galectin-3 were positively related to LVEF and LVEDD; Gal-3 and NT-ProBNP had the strongest correlation (r=0.57, P<0.01). The AUC of ROC for Gal-3 was 0.674 (0.584-0.763), for NT-proBNP was 0.837 (0.771-0.902) and for LVEF was 0.806, (0.735-0.878) which implied that NT-proBNP was the most powerful parameter for estimating HF. Conclusion: Gal-3 had the ability to estimate HF and could be used as a biomarker, while its ability was lower than NT-proBNP in clinical practice.
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<p><b>OBJECTIVE</b>To explore the effects of body mass index (BMI) and the levels of serum inflammatory cytokines on asthma control in children with asthma.</p><p><b>METHODS</b>One hundred and sixteen children with asthma were divided into three groups: normal (n=59), thin (n=31), and obesity (n=26) based on their BMI. The levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were determined using ELISA, and the level of high-sensitivity C-reactive protein (hs-CRP) was measured by immunoturbidimetric assays. Asthma control status in each group was evaluated by the Childhood Asthma Control Test (C-ACT) after 4 weeks of treatment.</p><p><b>RESULTS</b>The serum levels of IL-6, hs-CRP, and TNF-α were highest in the obesity group, followed by the thin group and the normal group (P<0.05), while the C-ACT score was highest in the normal group, followed by the thin group and obesity group (P<0.05). The normal group had significantly higher complete controlled and partially controlled rates than the thin and obesity groups (P<0.05); however, there were no significant differences between the thin and obesity groups (P>0.05). The levels of IL-6, hs-CRP, and TNF-α were negatively correlated with the C-ACT score (P<0.05). There were no significant correlations of BMI with the C-ACT score and levels of IL-6, hs-CRP, and TNF-α (P>0.05).</p><p><b>CONCLUSIONS</b>When BMI is too high or too low, the levels of serum inflammatory cytokines are all increased, which is harmful to asthma control. Maintaining a healthy weight in children with asthma may reduce the levels of serum inflammatory cytokines and improve the asthma control rate.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Asthma , Allergy and Immunology , Therapeutics , Body Mass Index , C-Reactive Protein , Cytokines , Blood , Interleukin-6 , Blood , Tumor Necrosis Factor-alpha , BloodABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical and SLC2A1 gene mutation characteristics of glucose transporter type 1 deficiency syndrome.</p><p><b>METHOD</b>The detailed clinical manifestations of six cases were recorded. The laboratory tests including EEG, MRI, blood chemistry, and lumbar puncture were performed. SLC2A1 gene mutations were analyzed by PCR, DNA sequencing and multiplex ligation-dependent probe amplification (MLPA).</p><p><b>RESULT</b>Patient 1, 2 and 3 had classical clinical symptoms including infantile onset seizures, development delay. Patient 4, 5 and 6 had non-classical clinical symptoms including paroxysmal behavior disturbance, weakness, ataxia, lethargy, especially after fasting or exercise, without severe seizures. The plasma glucose levels were normal. The CSF glucose levels decreased in all the six cases, ranged from 1.10 mmol/L to 2.45 mmol/L, the mean level was 1.68 mmol/L. The CSF glucose/plasma glucose ratios decreased, ranged from 0.16 to 0.51, the mean ratio was 0.34. Four patients had normal EEG. Two patients had focal and diffuse epileptiform discharge, and one of them also had paroxysmal occipital or generalized high-amplitude slow waves during awake and sleep time. MRI abnormalities were found in three patients, patient 1 with mild brain atrophy, patient 3 with bilateral ventricle plump, and patient 4 with high signals in T2 in the frontal and occipital white matter, interpreted as hypomyelination. SLC2A1 gene mutations were found in six cases. Patient 1 has large scale deletion in exon 2. In patient 2 to 6, the mutations were c.741 G>A (E247K), 599delA, 761delA, c.1148 C>A (P383H), c.1198 C>T (R400C) respectively. Two patients were treated with ketogenic diet. The seizures disappeared and development became normal. Three patients responded to frequent meals with snacks. One patient refused any treatments, the symptoms continued to exist.</p><p><b>CONCLUSION</b>The clinical manifestations of glucose transporter type 1 deficiency syndrome are varied. The common symptoms included infantile onset seizures and various paroxysmal events. These neurologic symptoms generally fluctuated and were influenced by factors such as fasting or fatigue. This feature could be a very important clue for the diagnosis of GLUT1-DS. Lumbar puncture is recommended in patients with episodic CNS symptoms especially after fasting. GLUT1-DS is a treatable neurometabolic disorder, early diagnosis and treatment may improve the prognosis of the patients.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Biomarkers , Brain , Diagnostic Imaging , Pathology , Carbohydrate Metabolism, Inborn Errors , Diagnosis , Genetics , Therapeutics , DNA Mutational Analysis , Diet, Ketogenic , Electroencephalography , Epilepsy , Diagnosis , Genetics , Therapeutics , Follow-Up Studies , Glucose Transporter Type 1 , Genetics , Magnetic Resonance Imaging , Monosaccharide Transport Proteins , Genetics , Movement Disorders , Diagnosis , Genetics , Therapeutics , Mutation , Genetics , RadiographyABSTRACT
Objective To analyze clinical diagnosis and treatment,aldehyde dehydrogenase 7 family member A1 (ALDH7A1) gene mutations in 1 Chinese child with pyridoxine dependent epilepsy(PDE).Methods The clinical manifestations and course of treatment were observed in a PDE patient with early epilepsy onset.Video-electroencephalogram(VEEG) and magnetic resonance imaging (MRI) were performed.The mutations of ALDH7A1 gene were examined.Results At the age of 2 months,recurrent epileptic seizures occurred and the child was resistant to antiepileptic drugs.Patient hospitalized several times due to frequent seizures and pyridoxine was used intravenously for several days.For each hospital stay,the frequent seizures were controlled completely under the treatment of pyridoxine and antiepileptic drugs.Seizures recurred at intervals of 13,14 and 38 days due to the treatment with antiepileptic drugs only without pyridoxine.Continuing oral pyridoxine without anticonvulsants led to seizure free for 5 months.No epileptiform discharges were found during several interictal VEEG monitoring and MRI showed normal.ALDH7A1 gene mutation analysis revealed two heterozygote mutations:c.410G > A (p.G137E) in exon 5 that was transmitted from the father,and IVS11 + 1G > A in intron 11 transmitted from the mother.Conclusions Early onset seizures have better response to pyridoxine and recurred after pyridoxine withdrawal in the patient,which suggested that he is a PDE patient.The interictal normal EEG could not rule out the possibility of PDE.This is the first report on ALDH7A1 mutations in PDE patient in China.Both the c.410G > A(p.G137E) and IVS11 + 1G > A mutations have not been reported previously.
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<p><b>OBJECTIVE</b>Children with refractory epilepsy who suffered from severe liver function impairment during valproic acid (VPA) treatment at routine dosage were studied. The clinical manifestations and therapeutic approaches were investigated in order to improve its diagnosis and management.</p><p><b>METHOD</b>Clinical information as well as features and management of 4 inpatients who were suffered from intractable epilepsy with severe liver function impairment induced by VPA since 2006 were collected and analyzed, including age of onset of epilepsy, VPA using age and the time when liver injury occurred, clinical manifestations, auxiliary examinations and management.</p><p><b>RESULT</b>Among the 4 cases, three were male and one was female. The admitted age ranged from 1 - 9 years and 1 month. The course of disease was 25 d - 6 months. They manifested as refractory epilepsy of epilepsia partialis continua which was difficult to control. After using VPA for 62 d (50 - 76 d), all developed severe impairment of liver synthetic function which was not related to the concentration of VPA. One was diagnosed with Alpers syndrome, two were suspicious of Alpers syndrome, and the other was diagnosed gliocytoma after brain biopsy. VPA was stopped immediately and symptomatic therapies were used. Other than that, intravenous injection of L-carnitine in 3 cases recovered the liver function.</p><p><b>CONCLUSION</b>VPA-associated severe hepatotoxicity can manifest first as impaired liver synthetic function. Besides alanin transaminase and aspartate transaminase, the liver synthetic function test is more important than monitoring of liver enzymatic functions in monitoring for the hepatotoxicity. Intravenous injection of L-carnitine in early stage showed good treatment effect.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Anticonvulsants , Biomarkers , Blood , Carnitine , Therapeutic Uses , Chemical and Drug Induced Liver Injury , Drug Therapy , DNA Mutational Analysis , Diffuse Cerebral Sclerosis of Schilder , Drug Therapy , Genetics , Epilepsy , Drug Therapy , Liver , Pathology , Liver Function Tests , Retrospective Studies , Valproic AcidABSTRACT
<p><b>OBJECTIVE</b>To summarize the phenotypes and identify SCN1A mutations in families with generalized epilepsy with febrile seizures plus (GEFS(+)), and analyze the genotype- phenotype correlations in GEFS(+) families.</p><p><b>METHOD</b>Genomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS(+) families. The phenotypes of the affected members were analyzed. The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing.</p><p><b>RESULT</b>In 39 GEFS(+) families, there were 196 affected members, ranging from 2 to 22 affected members in each family. Their phenotypes included febrile seizures (FS) in 92(46.9%), febrile seizures plus (FS(+)) in 62(31.6%), FS or FS(+) with partial seizures in 12(6.1%), afebrile generalized tonic-clonic seizures (AGTCS) in 11(5.6%), myoclonic atonic epilepsy in 8(4.1%), Dravet syndrome in 2(1.0%), childhood absence epilepsy in 1 (0.5%), FS(+) with myoclonic seizures in 1(0.5%), AGTCS and myoclonic seizures in 1 (0.5%), partial seizures in 1 (0.5%), unclassified seizures in 5 (2.6%). Four families were found with SCN1A mutations, including three families with missense mutation (N935H, R101Q, G1382R) and one family with truncation mutation (C373fsx378). In three families with missense mutations, the phenotypes include FS, FS(+), FS(+) with partial seizures, and AGTCS. In one family with truncation mutation, the phenotypes included FS, FS(+), and Dravet syndrome. The mother of proband in the family with missense mutation (R101Q) and the father of proband in the family with truncation mutation (C373fsx378) were both somatic mosaicism. Both of their phenotypes were FS(+).</p><p><b>CONCLUSION</b>The most common phenotypes of GEFS(+) were FS and FS(+), followed by the FS/FS(+) with partial seizures and AGTCS. The most severe phenotype was Dravet syndrome. SCN1A mutation rate in GEFS(+) was about 10%. Missense mutation was common in GEFS(+) families, few with truncation mutation. Few members of GEFS(+) families had somatic mosaicism of SCN1A mutations and their phenotypes were relatively mild.</p>
Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Base Sequence , DNA Mutational Analysis , Epilepsies, Myoclonic , Genetics , Epilepsy, Generalized , Genetics , Genotype , Molecular Sequence Data , Mutation , Genetics , Mutation, Missense , Genetics , Pedigree , Phenotype , Seizures, Febrile , GeneticsABSTRACT
<p><b>OBJECTIVE</b>The study was designed to examine the clinical and electroencephalographic characteristics of children with Jeavons syndrome.</p><p><b>METHOD</b>Video-electroencephalography (VEEG) monitoring was carried out in 9 patients with Jeavons syndrome. The clinical and electroencephalographic characteristics, treatment and prognoses were analyzed.</p><p><b>RESULT</b>Of the 9 patients, 8 were female, and 1 was male. The onset age of children with eyelid myoclonia (EM) was from 3 to 9 years old. It was obtained through the chief complaint, prosecution or VEEG monitoring. Three cases were misdiagnosed and 2 cases were overlooked initially. Seven out of 9 patients had generalized tonic clonic seizures (GTCS) during the course of disease, of whom 5 experienced only one episode. GTCS was the cause for the first visits to hospital in 5 patients. Since the clinical manifestations of EM with or without absence were often slight, VEEG monitoring with eye closure and intermittent photic stimulation tests helped to induce discharges and seizures. Eye closure was more potent than intermittent photic stimulation as a triggering factor. Ictal EEG showed 3 - 6 Hz generalized spike and waves and polyspikes burst. The main treatment option was valproate monotherapy (6 cases) or combined with other antiepileptic drugs (1 case). Levetiracetam, lamotrigine and topiramate were also used in patients and effective to some degree. Two patients lost follow up. The age of 7 patients at follow-up ranged from 9 y to 15 y. Seizures were controlled in 1 case, suspiciously controlled in 1 case, decreased in frequency in 4 cases and were still frequent in 1 case. During follow-up, normal intelligence was found in the former 2 cases, difficult learning in 2 cases, and slightly intellectual impairment in 2 cases.</p><p><b>CONCLUSION</b>Jeavons syndrome is one of the idiopathic generalized epilepsies characterized by EM with or without absence. The age of seizure onset might be difficult to be exactly established, as EM was often misinterpreted and overlooked initially. Clinical history combined with VEEG monitoring with eye closure and intermittent photic stimulation tests could diagnose this disease. Valproate and other new antiepileptic drugs were effective for this disease. Jeavons syndrome is a lifelong disorder. Seizures sometimes could be well controlled. When seizures were resistant to treatment, cognitive and intellectual impairment might occur.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Age of Onset , Anticonvulsants , Therapeutic Uses , Electroencephalography , Electromyography , Epilepsies, Myoclonic , Diagnosis , Drug Therapy , Epilepsy, Tonic-Clonic , Diagnosis , Drug Therapy , Eyelids , Follow-Up Studies , Myoclonus , Diagnosis , Drug Therapy , Photic Stimulation , Methods , Retrospective Studies , Seizures , Syndrome , Valproic Acid , Therapeutic UsesABSTRACT
This study reviews a case of mitochondrial respiratory chain complex I deficiency due to the 10191T>C mutation in mitochondrial ND3 gene. The previously healthy boy progressively presented with blepharoptosis, weakness, epilepsy and motor regression at age 6 years. Elevated blood lactate and pyruvate were observed. Brain magnetic resonance imaging showed symmetrical lesions in the basal ganglia. Leigh syndrome was thus confirmed. The protein from the mitochondria and genomic DNA of the boy and his parents was collected from peripheral blood leucocytes for the activity test for mitochondrial complex I to V and genetic analysis. The results showed the activity of complex I (33.1 nmol /min in 1 milligram mitochondrial protein) was lower than normal reference value (44.0±5.4 nmol /min in 1 milligram mitochondrial protein). The ratio of complex I to citrate synthase (19.8%) was also lower than normal reference value (48%±11%). The activities of complexes II to V were normal. 10191T>C mutation in ND3 gene of mitochondria was identified in the boy. 10191T>C mutation and complex I deficiency were not detected in his parents. At present, he is 16 years old, and of normal intelligence with spastic paralysis in both lower extremities after treatment. It is concluded that a Chinese boy with isolated complex I deficiency due to 10191T>C mutation in ND3 gene was firstly diagnosed by peripheral leukocytes mitochondrial respiratory chain enzyme assay and gene analysis. This study can provide clinical data for the nosogenesis of Leigh syndrome.
Subject(s)
Adolescent , Humans , Male , Brain , Pathology , Electron Transport Complex I , Genetics , Leigh Disease , Genetics , Magnetic Resonance Imaging , Mitochondrial Diseases , Genetics , MutationABSTRACT
<p><b>OBJECTIVE</b>To study SCN1A gene mutations and their inheritance in patients with Dravet syndrome(DS), and to analyze the phenotypes of their family members and genotype-phenotype correlations.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples from 181 DS patients and their parents. Phenotypes of affected members were analyzed. SCN1A gene mutations were screened using PCR-DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) RESULTS: SCN1A gene mutations were identified in 128 patients (70.7%), which included 60 missense mutations (46.9%), 55 truncation mutations (43.0%), 10 splice site mutations (7.8%), and 3 cases with SCN1A gene fragment deletions or duplications(2.3%). Five patients (3.9%) had mutations inherited from one of their parents. One father has carried a somatic mutation mosaicism (C373fsx378). For the 5 parents carrying a mutation, 1 had febrile seizures, 2 had febrile seizures plus, 1 had afebrile generalized tonic-clonic seizures, whilst 1 was normal.</p><p><b>CONCLUSION</b>The mutation rate of SCN1A in DS patients is about 70%. Most mutations are of missense and truncation mutations. Only a few patients have carried fragment deletions or duplications. Most SCN1A mutations are de novo, only a few were inherited from the parents. SCN1A mutations carried by the parents can be in the form of mosaicism. The phenotypes of parents with SCN1A mutations are either mild or normal.</p>
Subject(s)
Female , Humans , Male , Amino Acid Sequence , Base Sequence , Epilepsies, Myoclonic , Genetics , Genetic Association Studies , Genotype , Molecular Sequence Data , Mutation , Genetics , Pedigree , Phenotype , Sequence AlignmentABSTRACT
<p><b>OBJECTIVE</b>To summarize the electroclinical characteristics of myoclonic atonic epilepsy (MAE) in children.</p><p><b>METHOD</b>The clinical data, video electroencephalogram (EEG) and simultaneous electromyography (EMG) of MAE patients were analyzed. The treatment and its effects were followed up.</p><p><b>RESULT</b>In 47 MAE patients, 25 had a history of febrile seizures (FS), 20 had a family history of FS or epilepsy. All patients had a normal development before the illness. The age of afebrile seizure onset was between 1.4 years to 5.8 years. The first seizure was generalized tonic-clonic seizure (GTCS) in 41 patients (87.2%). All patients had multiple seizure types, including 47 GTCS (97.9%), 34 myoclonic atonic seizures (72.3%), 47 myoclonic seizures (100%), 32 atonic seizures (68.1%), 36 atypical absences (76.6%) and 3 tonic seizures (6.4%). EEG backgrounds were slow or parietal θ rhythm, interictal EEG showed 1-4 Hz (predominant 2-3 Hz) generalized spike and wave or poly spike and wave discharges in all cases. Seizures were controlled by antiepileptic drugs (AEDs) in 41 patients (87.2%). Valproate was used in 37. Lamotrigine was used in 26. Mild mental retardation was observed in 10 children after the onset of the illness.</p><p><b>CONCLUSION</b>The clinical features of MAE included the following: the development was normal before the onset of the illness; the onset of seizure type was often GTCS. All patients had multiple generalized seizure types. Myoclonic atonic seizure was its characteristic seizure type. EEG showed generalized discharges. Early diagnosis and rational choice of AEDs are important for getting a better prognosis.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Electroencephalography , Epilepsies, Myoclonic , Diagnosis , Therapeutics , Epilepsy, Generalized , Diagnosis , TherapeuticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the value of cryptococcal latex agglutination test in the diagnosis and treatment of cryptococcal meningitis in children.</p><p><b>METHODS</b>The clinical data of 10 children with cryptococcal meningitis were retrospectively studied. Cryptococcal meningitis was confirmed based on clinical manifestations, India ink stain, cryptococcal latex agglutination test or cryptococcal culture. The outcome of antifungal treatment and the changes of latex agglutination test titer were followed up for 2 to 4 years.</p><p><b>RESULTS</b>Latex agglutination test and/or India ink stain were positive (titer 1 : 64-1 : 1024) in 8 patients in the first examination of cerebrospinal fluid. In the other 2 patients, latex agglutination test was positive (titer 1 : 256) in the fourth examination of cerebrospinal fluid in one, and India ink stain was positive in the eleventh examination in the other. After antifungal treatment, six patients were cured, two patients died, and two patients were lost to follow-up. The positive cryptococcal latex agglutination test (titer 1 : 2-1 : 16) was seen respectively in six, three, two and one cured patients 6 months, 1 year, 2 years and 4 years later.</p><p><b>CONCLUSIONS</b>The cryptococcal latex agglutination test of cerebrospinal fluid is valuable for the quick and early diagnosis of cryptococcal meningitis; however, the decision of withdrawal of antifungal treatment should not rely on the results of the test.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Follow-Up Studies , Latex Fixation Tests , Methods , Meningitis, Cryptococcal , Cerebrospinal Fluid , Diagnosis , Drug TherapyABSTRACT
The idiopathic generalized epilepsies (IGE) comprise two major groups: the classical IGE and generalized epilepsy with febrile seizures plus (GEFS+). The classical IGE syndromes include childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and epilepsy with generalized tonic-clonic seizures alone. GEFS+ is a familial epilepsy syndrome, characterized by a spectrum of phenotypes. The phenotypes of GEFS+ include febrile seizures (FS), febrile seizures plus (FS+), FS/ FS+ and absences, myoclonic, atonic or partial seizures, myoclonic-astatic epilepsy and severe myoclonic epilepsy of infancy. Our study of 121 individuals in 20 families, where 84 had previously recognized GEFS+ phenotypes, expands the phenotypic spectrum of GEFS+ syndrome to include afebrile generalized tonic-clonic seizures with generalized spike wave or normal EEG in the absence of FS. To date, there are three ion channel genes (SCN1A, SCN1B and GABRG2) confi rmed as having a role in GEFS+, but none has been implicated in the majority of patients with GEFS+ phenotypes, such as those found in small families. Indeed it is likely that in most families, GEFS+ is a polygenic disorder resulting from the cumulative effect of a number of genes of lesser effect rather than the genes so far characterized in the few large families ascertained. Small GEFS+ families and bilineal inheritance in some add support for complex inheritance in a signifi cant proportion of families. The phenotypes of classical IGE occur in some GEFS+ families. The percentage of classical IGE phenotypes is 9% (11/121) of affected individuals in our study. This suggests that classical IGE phenotypes and GEFS+ phenotypes overlap in some GEFS+ families. Our study provides new insights into the inter-relationship of GEFS+ and classical IGE, where shared genetic determinants probably account for the overlap of these syndromes in some families.
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<p><b>OBJECTIVE</b>Epilepsy with myoclonic absences (EMA) is a type of childhood epilepsy characterized by a specific seizure type, i.e. myoclonic absences (MA). This study aimed to investigate the clinical and electrophysiological characteristics of EMA.</p><p><b>METHOD</b>Video-EEG monitoring was carried out in 6 patients with EMA, and 2 of them were examined with simultaneous deltoid muscle surface electromyogram (EMG). The clinical and EEG characteristics, treatment and prognoses of EMA were analyzed.</p><p><b>RESULT</b>Of the 6 patients, 3 were female, and 3 were male. The age of onset was from 2 years and 3 months to 11 years (average 5 years and 2 months). MA was the sole seizure type in 5 patients. One patient presented generalized tonic clonic seizures (GTCS) at the onset and then switched to MA. The manifestations of MA included an impairment of consciousness of variable intensity, rhythmic myoclonic jerks with evident tonic contraction mainly involving the upper extremities, a deviation of head and body to one side or asymmetrical jerks observed in some cases, a duration ranging from 2 to 30 s, an abrupt onset and termination, a high frequency of attacks, at least several times to over 30 times per day, and easily provoked by hyperventilation. The ictal EEG consisted of rhythmic 3 Hz spike and wave discharges that were bilateral, synchronous and symmetrical in all patients. The deltoid muscle EMG recording in 2 patients showed rhythmic myoclonus at the same frequency as the spike and waves. The interictal EEG showed generalized spike and wave discharges in all patients, and focal discharges in some patients. Valproate was the drug of choice, which was often combined with other antiepileptic drugs. The ages at follow up ranged from 6 years and 4 months to 19 years. Seizures were controlled from 8 months to 3 years in 4 cases. The treatment at the onset was late in one case and was irregular in another who had GTCS during the course of the disease. These two cases were followed up for 2 years and 6 months and 5 years, respectively. Seizures could not be controlled in the 2 patients with intellectual impairment.</p><p><b>CONCLUSION</b>EMA was a rare type of childhood epilepsy characterized by MA. Clinical observation and ictal video-EEG and EMG were essential to diagnose EMA. Valproate alone or combined with other antiepileptic drugs given early could have a favorable effect to EMA. Delayed therapy and the presence of GTCS might suggest poor prognosis.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Electroencephalography , Electromyography , Epilepsies, Myoclonic , Diagnosis , Prognosis , Retrospective StudiesABSTRACT
The fluorescence spectroscopy and UV spectroscopy have been used to monitor the inclusion phenomena of VP-16 with beta-cyclodextrin (beta-CD), together with studies concerning the effects of reaction time, temperature and concentration on this behavior. The results show that the fluorescence intensity increased when VP-16 and beta-CD forming a 1 : 1 inclusion complex, which indicate that beta-CD has fluorescence sensitizing effect on the VP-16. At 22 degrees C, the inclusion constant was 2.63 x 10(5) L x mol(-1) at pH 7.0. VP-16 has maximum emission wavelength at 316 nm under the optimum conditions. According to this, the quantitative micro-detection method of VP-16 by fluorescence spectrometry was established. The linear regression equation was y = 1.107 89 x 10(70 x + 95.898 1, with a correlation coefficient of 0.999 9. The detection limit was 2.094 x 10(-7) mol x L(-1).
Subject(s)
Drug Interactions , Etoposide , Chemistry , Hydrogen-Ion Concentration , Linear Models , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , Temperature , beta-Cyclodextrins , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical, neurophysiologic characteristics and therapeutic considerations of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy of childhood (ABPE).</p><p><b>METHODS</b>Video-EEG monitoring with outstretched arm tests were carried out in 17 patients, and 9 of them were examined with simultaneous electromyography (EMG). The ENM manifestations, electrophysiologic features and responses to antiepileptic drugs (AED) were analyzed.</p><p><b>RESULTS</b>Seventeen patients were diagnosed as having benign childhood epilepsy with centrotemporal spikes (BECT) during the early course of the disease and were treated with AED. During the course of the disease, hand trembling, objects dropping, head nodding and instability during standing might be clues for ENM occurrence. ENM had been confirmed in our patients by outstretched arm tests during video-EEG recording. The ictal EEG showed that high-amplitude spikes followed by a slow wave over the contralateral motor areas. This was further confirmed by time-locked silent EMG in 9 patients. During ENM occurrence or recurrence, the habitual seizures and interictal discharges were exaggerated. Atypical absence seizures also occurred in 6 patients. The alteration of therapeutic options of AED relating to ENM appearance in some patients included the add-on therapy with carbamazepine (CBZ), oxcarbazepine, phenobarbital, or withdrawal of valproate (VPA). ENM was controlled in most cases by using VPA, clonazepam (CZP) and corticosteroid with different combination.</p><p><b>CONCLUSION</b>ENM could occur during the course of ABPE. Outstretching arm tests during video-EEG monitoring in combination with EMG was essential to confirm ENM. The ENM occurrence was always associated with the frequency increasing of habitual seizures and the aggravation of interictal discharges. Some AED such as CBZ might induce ENM. VPA, benzodiazepines and corticosteroid with different combination were relatively effective in treatment of ENM.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Anticonvulsants , Therapeutic Uses , Electroencephalography , Electromyography , Epilepsies, Myoclonic , Drug Therapy , Epilepsies, Partial , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>Severe myoclonic epilepsy of infancy (SMEI), or Dravet syndrome, is a severe epileptic encephalopathy. This study aimed to investigate the clinical features and genetic diagnosis of SMEI.</p><p><b>METHODS</b>The electroclinical data and the mutation of SCN1A gene in 13 children with SMEI were analyzed.</p><p><b>RESULTS</b>Of the 13 children, 10 were males and 3 were females. Eight of them had family history of febrile seizures. The average age of seizure onset was 5.6 months, with a range of 2 to 9 months. The initial seizure was a febrile seizure in 9 patients (69%). Generalized or hemiclonic seizures were often triggered by fever. Eight patients had a history of febrile status. Afebrile seizures occurred from 2 months to 21 months of age. All patients went on to develop multiple seizure types. Generalized tonic clonus seizures (GTCS) were found in 11, partial seizures in 12, atypical absence in 10. Myoclonic seizures were presented in all patients. Twelve patients had 3 or more seizure types. Seizures of all patients had a characteristic of temperature sensitivity. The precipitating factors included fever, hot bath and vaccination. Nine patients (69%) had a history of status epilepticus. Delay in mental development was present in 11 cases, ataxia in 5 and pyramidal sign in 2. EEG was normal in most patients in the first year of life, followed by generalized, focal and multifocal discharges. Brain MRI was abnormal in 2 cases. Seizures were not completely controlled in all patients. Carbamazepine and lamotrigine aggravated seizures in some patients. SCN1A gene mutation was found in 10 cases, including seven missense mutations, two nonsense mutations and one frame shift mutation.</p><p><b>CONCLUSION</b>The clinical features of SMEI were seizure onset within one year of age, first event is often a febrile seizure; multiple seizure types and mental delay occurred after the second year of life; seizures have a characteristic of temperature sensitivity; EEG was normal in the first year of life, followed by generalized, focal or multifocal discharges; early diagnosis by testing SCN1A mutation guides selection of antiepileptic drugs.</p>
Subject(s)
Child, Preschool , Female , Humans , Infant , Male , DNA Mutational Analysis , Electroencephalography , Epilepsies, Myoclonic , Diagnosis , Genetics , Genetic Testing , Mutation , Nerve Tissue Proteins , Genetics , Sodium Channels , GeneticsABSTRACT
<p><b>OBJECTIVE</b>Clinical manifestations of opsoclonus-myoclonus syndrome (OMS) in children were summarized and analyzed and the clinical features and therapeutic approaches to OMS were investigated in order to improve its diagnosis and management.</p><p><b>METHODS</b>Clinical information on features and management of 6 cases with OMS inpatients being followed up from 2006 to 2007 were collected and analyzed.</p><p><b>RESULTS</b>Among the 6 cases, one was male and the other five were female. The age at the onset ranged from 12 to 26 months (average 21.0 months). Four of them had history of prior infection. The symptoms were opsoclonus, myoclonus, ataxia, sleep disturbances and behavioural problems in the 6 cases. Urinary DL-3-methoxy-4-hydroxy-acid amygdalin (VMA) was positive in 1 case. Abdominal B-mode ultrasound showed a mild hepatomegaly in 4 cases. The EEG showed abnormal findings such as slow background activity in 3 cases. Epileptiform discharges were found in none of the patients. MRI showed a high signal in medial longitudinal fasciculus and tectospinal tract on T2-weighted image in 1 case. Computerized tomography found L3-4 arachnoid cysts in 1 case and was normal in the others. Adrenocorticotropic hormone (ACTH) was given to all these patients and was effective in all during acute stage. In 2 cases the disease relapsed during follow-up stage.</p><p><b>CONCLUSION</b>OMS is a rare neurological condition with opsoclonus, myoclonus, ataxia, sleep disturbances and behavioral problems, which might relapse easily and is associated with adverse neurological outcome. ACTH therapy is effective in management of OMS.</p>
Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Adrenocorticotropic Hormone , Therapeutic Uses , Opsoclonus-Myoclonus Syndrome , Diagnosis , Therapeutics , Prognosis , Recurrence , Treatment OutcomeABSTRACT
To investigate the components in Plastrum Testudinis which have effects on the proliferation of rat bone marrow mesenchymal stem cells( bMMSCs), the active parts of plastrum testudinis which can promote proliferation of rat mesenchymal stem cells were extracted by petroleum aether. The activities of inducing the proliferation of bMMSCs were studied by MTT assay and flow cytometry. The chemical components of extraction were analyzed by GC-MS. The results showed that the petroleum aether extraction can obviously promote the proliferation of the stem cells. The main components are long-chain fatty acids, cholesterols and cholest-4-en-3-one, and palmitic acid, stearic acid and cholest-4-en-3-one have effects on proliferation of bMMSCs. In plastrum testudinis, fatty acids can promote the proliferation of bMMSCs but not increase overly. This provide the experiment basis, and offer important reference for Traditional Chinese Medicine that researches stem cells.
Subject(s)
Animals , Rats , Bone Marrow Cells , Cell Biology , Cell Proliferation , Cells, Cultured , Fatty Acids , Pharmacology , Materia Medica , Chemistry , Pharmacology , Mesenchymal Stem Cells , Cell Biology , TurtlesABSTRACT
<p><b>OBJECTIVE</b>Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive leukoencephalopathy. Few reports of PMD patients without genetic confirmation have been published in the mainland of China. The clinical and genetic features of a family with PMD were analyzed, which may contribute to definite diagnosis, genetic counseling and prenatal diagnosis of this rare hereditary disease in China.</p><p><b>METHODS</b>Clinical data of the proband and other family members as well as 14 DNA samples were collected. Clinical features including symptoms, signs and cranial MRI were analyzed. Multiplex ligation-dependent probe amplification (MLPA) assays were performed to detect PLP1 duplication, which helps identify the type of PLP1 mutation in this family and the genotype-phenotype correlations.</p><p><b>RESULTS</b>(1) The proband and the other 3 male patients in the family presented with nystagmus, motor retardation followed by regression. The cranial MRI of proband showed evidence of poor myelination with diffused high signal in white matter region on T2-weighed image and reduced amount of white matter in volume, which is consistent with the typical features of cranial MRI in PMD. (2) PLP1duplication was identified in the proband. Combined with the clinical features of the proband and other patients in this family, the diagnosis of classic form of PMD was confirmed. Another 3 females with normal phenotype in the family were proved to be carriers of PLP1duplication.</p><p><b>CONCLUSIONS</b>(1) The Classic form of PMD in this pedigree is resulted from the PLP1 duplication, which is consistent with the previously reported genotype-phenotype correlations; (2) The results serve as an evidence for reliable genetic counseling and prenatal diagnosis for this family. (3) MLPA, which is a newly developed method, is a rapid and reliable technique to detect the whole gene duplication of PLP1.</p>