Clinical and molecular genetic analysis of Angelman syndrome with oculocutaneous albinism type 2: A case report and literature review / 北京大学学报(医学版)

To summarize the clinical diagnosis and treatment process and genetic test results and characteristics of one child with Angelman syndrome (AS) complicated with oculocutaneous albinism type 2 (OCA2), and to review the literature. "Angelman syndrome" "P gene" and "Oculocutaneous albinism type 2" were used as keywords to search at CNKI, Wanfang, and PubMed databases (from creation to December 2019). Then all the patients were analyzed. The patient in this study was a girl aged 1 year. After birth, she was found to present as white body, yellow hair, and nystagmus. She could raise her head at the age of 2 months and turn over at the age of 7 months. The head circumference was 42 cm and she could not sit alone or speak at present. Trio-based exome sequencing revealed that the patient carried a homozygous mutation of c.168del (p.Gln58ArgfsTer44) in the P gene, and her father was heterozygous and her mother was wild-type. The detection of copy number variation showed deletion on the maternal chromosome at 15q11.2-13.1 region (P gene located in this region) in the patient. Until December 2019, a total of 4 cases in the 4 literature had been reported. Adding our case here, the 5 cases were summarized and found that all the cases showed white skin, golden hair, and shallow iris after birth. Comprehensive developmental delay was found around 6 months of age after birth, and the language remained undeveloped in 2 cases till follow-up into childhood. Seizures occurred in 4 patients. Two cases had ataxia. All the 5 cases had acquired microcephaly. Two cases had a family history of albinism. Electroencephalogram monitoring was completed in 3 cases and the results were abnormal. Genetic tests showed that all the 5 cases had deletion on maternal chromosome at 15q11-13 region. Four cases carried mutation of P gene on paternal chromosome. And 1 case was clinically diagnosed as OCA2 without P gene test. AS combined with OCA2 is relatively rare. OCA2 is easily diagnosed based on the obvious clinical manifestations after birth. When combined with clinical manifestations such as neurodevelopmental delay, it might indicate the possibility of AS that is hardly diagnosed clinically at an early stage. Genetic tests can reveal the cross-genetic phenomenon of AS and OCA2 and the complex of them can be eventually diagnosed.

Clinical phenotypes and genetic features of epilepsy children with MBD5 gene variants / 中华儿科杂志

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.

Photosensitive tonic-clonic seizures:a continuum between focal and generalized seizures / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether the tonic-clonic seizure (TCS) induced by intermittent photic stimulation (IPS)was generalized tonic-clonic seizure (GTCS)or partial secondarily tonic-clonic seizure (PGTCS),and to analyze the relationship between them.@*METHODS@#Video-electroencephalogram (VEEG)database of Peking University First Hospital from March 2010 to October 2018 were reviewed. Fifteen cases with idiopathic epilepsy who had TCS induced by IPS were included in this study, and their clinical and electroencephalogram (EEG)characteristics were retrospectively analyzed.@*RESULTS@#In this study, 4 of the 15 cases were boys and 11 were girls. The age of seizure onset ranged from 1 to 13 years. According to the medical records: 12 cases were considered as GTCS,while the remaining 3 cases were considered as PGTCS. The age at VEEG monitoring ranged from 2.5 to 16.0 years. All backgrounds of the VEEG were normal. Interictal discharges:generalized discharges in 11 cases, of which 4 cases coexisted with posterior discharges, 2 cases coexisted with Rolandic discharges, the other 5 cases merely had generalized discharges; merely focal discharges in two cases, one in the Rolandic area and the other in the posterior area; no interictal discharge in the remaining 2 cases. IPS induced photoparoxysmal response (PPR)results: 2 cases without PPR,the remaining 13 cases with PPR of generalized discharges, and 6 of the 13 cases coexisted with posterior discharges. IPS induced photoconvulsive response (PCR)results: GTCS in one case (contradictory to medical history),PGTCS in 11 cases (consistent with medical history),and GTCS and PGTCS hardly to distinguish in the remaining 3 cases. Of the three conditions above, there were generalized myoclonic seizures induced by IPS before TCS in 7 cases.@*CONCLUSION@#The medical history was unreliable in determining whether TCS was generalized or focal. Myoclonic seizures can coexist with PGTCS, and sometimes GTCS was indistinguishable from PGTCS, indicating that the dichotomy of seizure types need to be improved. Photosensitive TCS should be regarded as a continuum between focal and generalized seizures.

Application of scalp-recorded high-frequency oscillations in epileptic encephalopathy with continuous spike-and-wave during sleep / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical significance of high-frequency oscillations (HFOs) on scalp electroencephalography (EEG) in patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS).@*METHODS@#Twenty-one CSWS patients treated for epilepsy from January 2006 to December 2016 in Pediatric Department of Peking University First Hospital were enrolled into the study. Selected clinical variables including gender, age parameters, seizure frequencies and antiepileptic drugs were compared between (a). HFO-positive group and HFO-negative group before methylprednisolone treatment and (b). excellent seizure outcome group and not-excellent seizure outcome group after methylprednisolone treatment. Interictal HFOs and spikes in pre- and post-methylprednisolone scalp EEG were measured and analyzed.@*RESULTS@#Before methylprednisolone treatment, there were 12 of 21 (57%) CSWS patients had HFOs, with a mean value 43.17 per 60 s per patient. The 12 patients with HFOs tended to have more frequent epileptic negative myoclonus/atonic/myoclonus/atypical absences than those without HFOs in a month before methylprednisolone treatment. A total of 518 HFOs and 22 592 spikes were found in the pre-methylprednisolone EEG data of 21 patients, and 441 HFOs (86%) were associated with spikes. The highest amplitudes of HFOs were significantly positively correlated with that of spikes (r=0.279, P<0.001). Rates reduced by methylprednisolone treatment were statistically significant for both HFOs (P=0.002) and spikes (P=0.006). The percentage of reduction was 91% (473/518) and 39% (8 905/22 592) for spikes and HFOs, respectively. The percentage of spike and HFOs changes was respectively 100% decrease and 47% decrease in the excellent seizure outcome group, and they were 79% decrease and 18% increase in the not-excellent seizure outcome group.@*CONCLUSION@#Prevalence of HFOs might reflect some aspect of epileptic activity. HFOs were more sensitive to methylprednisolone treatment than spikes and had a good correlation with the prognosis of seizures, and HFOs could be applied to assess epilepsy severity and antiepileptic therapy.

Clinical analysis of pyridoxine-dependent epilepsy in a child and ALDH7A1 mutation / 中华实用儿科临床杂志

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.

Diagnosis and treatment of epilepsy and narcolepsy comorbid / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical diagnosis and treatment process of narcolepsy and epilepsy co-existence, and thereby to improve awareness of such cases.</p><p><b>METHOD</b>The clinical manifestations of 2 cases were observed, and video-electroencephalogram (VEEG), multiple sleep latency tests (MSLT) were performed. Hypocretin 1 level in cerebrospinal fluid was examined in one case.</p><p><b>RESULT</b>The onset of disease of case one was started with epilepsy with myoclonic seizure. After half a year, catalepsy induced by emotion especially laughing and excessive daytime sleepiness appeared. MSLT was positive and hypocretin 1 level decreased. Narcolepsy-cataplexy was definitely diagnosed in this case. Valproate was given and seizure was controlled completely, but the excessive daytime sleepiness was aggravated. Combination of valproate, methylphenidate and clomipramine treatment improved the symptoms of narcolepsy and the patient was still free of epileptic seizures. The onset symptoms of case 2 were catalepsy and excessive daytime sleepiness. MSLT was positive. The treatment was ineffective because of bad compliance. After 2 years, episodes of impairment of consciousness with automatism occurred. VEEG showed slow waves and spikes in right temporal area. Complex partial seizure was determined. Oxcarbazepine was used and then the patients became seizures free, but the symptoms of narcolepsy were still obvious.</p><p><b>CONCLUSION</b>Comorbidity of narcolepsy and epilepsy is a rare phenomenon. Clinical symptoms, predisposing factor, VEEG and MSLT can help diagnosis and differential diagnosis. The antiepileptic drugs might aggravate drowsiness. Based on therapy of epilepsy by using antiepileptic drugs, low dosage of central nervous system stimulants might improve the drowsiness and catalepsy symptoms of narcolepsy.</p>

Clinical and electroencephalographic characteristics of Jeavons syndrome / 中华儿科杂志

<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>

Relationship between HBeAg seroconversion with genotypes and HBV specific CTL in patients with chronic hepatitis B treated with Adefovir dipivoxil / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore relationship between HBeAg seroconversion with HBV genotypes and HBV specific CTL in patients with chronic hepatitis B (CHB) treated with Adefovir dipivoxil.</p><p><b>METHODS</b>Seventy CHB patients had positive HBV DNA (HBV DNA > or = 1 x 10(4) copy/ml), 45 cases had positive HBeAg, of whom 23 cases (51. 11%) had genotype B, 22 cases (48.89%) had genotype C. ALT > 2 x upper limit of normal value (ULN), human leukocyte antigen (HLA)-A(n) positive, patients were treated with Adefovir dipivoxil (commercial name is Mingzheng, Zhengda Tianjing Pharmaceutical Company), 10 mg, orally, once a day. After treatment for 12 months, observe relationship between HBeAg seroconversion with HBV genotypes and HBV specific CTL.</p><p><b>RESULTS</b>After treatment with Adefovir dipivoxil for 12 months, HBV specific CTL (0.68% +/- 0.11%) was higher than that before treatment (0.33% +/- 0.11%), t = 8.36 P < 0.001, HBV DNA (3.01 +/- 0.2) log10 copy/ml was lower than that before treatment (6.27 +/- 0.70) log10 copy/ml, t = 12.63 P < 0.001, HBV DNA turned negative (< 500 copy/ml) 43 cases (61.43%), in 45 cases with positive HBeAg, HBeAg turned negative in 13 cases (28.89%), 8 cases had HBeAg seroconversion (17.78%), HBV specific CTL (0.86% +/- 0.05%) of patients with HBeAg seroconversion is higher than (0.61% +/- 0.07%) of patients without HBeAg seroconversion (37 cases, 82.22%) t = 7.88, P < 0.001. In 8 cases with HBeAg seroconversion, 7 cases had genotype B (30.43% of genotype B), 1 cases had genotype C (4.55% of genotype C), chi2 = 5.15, P < 0.05.</p><p><b>CONCLUSION</b>Adefovir dipivoxil can enhance HBV specific cellular immunity of CHB patients. After treatment, occurrence of HBeAg seroconversion is related to increase of HBV specific CTL level and may be related to genotypes.</p>

Electroclinical features of myoclonic-atonic epilepsy / 中华儿科杂志

<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>

Postoperative complications of acromioclavicular joint dislocation of Tossy III / 中国骨伤

<p><b>OBJECTIVE</b>To analyze retrospectively the postoperative complications of acromioclavicular joint dislocation (Tossy III) and explore the preventative methods for the complications.</p><p><b>METHODS</b>Forty-eight cases of acromioclavicular joint dislocation (Tossy III) were reviewed, 14 cases treated with open reduction and Kirschner wire combined with steel wire fixation (group A), 11 cases treated with open reduction and lag screw or steel wires fixation (group B), 23 cases treated with open reduction and AO clavicular hook plate fixation (group C). The acromioclavicular ligament, articular capsule, coracoclavicular ligament and coracoacromial ligament were repaired in all patients. The reasons of postoperative complications were analyzed.</p><p><b>RESULTS</b>Forty-eight patients got average follow-up of 18 months. In group A, 8 patients obtained excellent results, 4 good and 2 poor; in group B, 7, 3 and 1, respectively; in group C, 21, 1 and 1, respectively. The excellence rate showed statistical difference between group A and C (P < 0.05). In group A, 4 cases with postoperative pain, 3 cases with periarthritis of shoulder, 3 cases with arthritides of acromioclavicular joint, 4 cases with internal fixation failure and 2 cases with recurrence of joint dislocation; in group B, 3, 2, 1, 3 and 1, respectively; in group C, 22, 2, 1, 2 and 1, respectively. There was no significant difference in postoperative complications in three groups (P > 0.05).</p><p><b>CONCLUSION</b>Selection of the suitable internal fixation and reconstruction of coracoclavicular and coracoacromia ligaments is the basic operation. Acromioclavicular space debridement, ligamentous reconstruction, rigid internal fixation are effective methods to reduce postoperative complications for the treatment of acromioclavicular joint dislocation.</p>

Clinical and electroencephalographic characteristics of epilepsy with myoclonic absences / 中华儿科杂志

<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>

Effect of eyes closure, eyes closed and photic stimulation on the epileptiform discharges in children with epilepsies / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of eyes closure and closed on the epileptiform discharges, and the relationship between eyes closure or closed sensitivity and photosensitivity.</p><p><b>METHODS</b>During video-EEG monitoring, open-close eyes tests and intermittent photic stimulation (IPS) under different eyes conditions were carried out in epilepsy patients. The eyes conditions were divided into eyes opened, eyes closure (the period immediately after closing of the eyes and only lasts for less than 3 s), and eyes closed (the period lasting for more than 3 s and persisting as long as the eyes remain closed). From 135 patients, 13 cases whose EEG showed eyes closure or closed sensitivity had been selected out for our study. The clinical, eyes closure or closed sensitivity and the relationship between eyes closure or closed sensitivity and photosensitivity were analyzed.</p><p><b>RESULTS</b>Of the 13 patients, 8 were female, and 5 were male. The age ranged from 6 years to 17 years (median 11 years). The age at onset of epilepsy ranged from 1.5 years to 14.5 years (median 9 years). Epileptiform discharges could be provoked by eyes closure in 10 of 13 patients, associated with photosensitivity in 8 patients. Of the 8 patients, 6 cases showed photosensitivity under eyes closure and only 4 cases showed photosensitivity under eyes closed. Eyes closed sensitivity had been seen in 3 patients, with photosensitivity in 2 patients. Evoked EEG patterns and discharges regions by eyes closure and eyes closed conditions had not obvious differential and might be strongly related to the types of epilepsies. The intensity and frequencies of photosensitivity under different eyes conditions were different. After valproate acid treatment, the eyes closure or closed sensitivity and photosensitivity improved in 4 cases, with improvement of photosensitivity prior to eyes conditions sensitivity.</p><p><b>CONCLUSIONS</b>Eyes closure and eyes closed could induce EEG paroxysms, which involved in some types of epileptic syndromes and appeared common in female patients. Eyes closure or closed sensitivity might coexist or be disassociated with photosensitivity. Testing eyes closure, eyes closed and IPS during EEG monitoring would contribute to finding the EEG discharges, further help to diagnose epilepsies and epileptic syndromes and guide treatment.</p>

Clinical features and SCN1A gene mutation analysis of severe myoclonic epilepsy of infancy / 中华儿科杂志

<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>

Relationship among eye condition sensitivities, photosensitivity and epileptic syndromes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Electroencephalogram (EEG) activity in normal subjects and epileptic patients is often closely related to the eye's status such as eye opened (EO), eye closure (ECL) and eyes closed (EC). ECL is the period immediately after closing of the eyes and only lasts for less than 3 seconds if the eyes remain closed. EC is the period as long as the eyes are closed. Epileptiform changes on EEG induced by ECL or EC are called the changes of ECL sensitivity (ECLS) or EC sensitivity (ECS). ECLS occurs mainly but not exclusively in photosensitive patients and ECS has been seen rarely in photosensitive patients. This study aimed to investigate the relationships among ECLS, ECS, photosensitivity and epilepsy syndromes in children.</p><p><b>METHODS</b>EEG records from child patients in the EEG Department of Peking University First Hospital during the period of May 2005 to May 2007 were examined for the presence of ECLS or ECS. Open-close eye tests and intermittent photic stimulations were carried out during video-EEG monitoring for examining ECLS, ECS and photosensitivity.</p><p><b>RESULTS</b>Based on ECLS and ECS on their EEGs, 30 patients were divided into ECLS group (16 cases) and ECS group (14 cases). There were more boys than girls in the two groups. The mean age of initial detection of ECLS and ECS was 10 years, and the average onset age of seizures was 9 years. The epilepsy syndromes in the ECLS group included idiopathic photosensitive occipital lobe epilepsy, Panayiotopoulos syndrome, symptomatic occipital lobe epilepsy, juvenile myoclonic epilepsy, juvenile absence epilepsy, eyelid myoclonia with absences, epilepsy with grand mal on awakening and pure photosensitive epilepsy with mainly generalized tonic clonic seizures. Those in the ECS group were juvenile myoclonic epilepsy, idiopathic photosensitive occipital lobe epilepsy, Panayiotopoulos syndrome and Gastaut type-idiopathic children occipital epilepsy. Photosensitivity was detected in 88% of patients with ECLS and 29% of patients with ECS.</p><p><b>CONCLUSIONS</b>ECLS and ECS are relatively common in females. Comparing with ECS, ECLS is found in more epilepsy syndromes. However, ECS and ECLS could exist in the same epilepsy syndrome. ECLS and ECS can be associated or dissociated with photosensitivity. The rate of ECLS with photosensitivity is higher than that of ECS with photosensitivity, suggesting that mechanisms for ECLS, ECS and photosensitivity may be different but correlated.</p>

Clinical and electrophysiologic studies on epileptic negative myoclonus in atypical benign partial epilepsy of childhood / 中华儿科杂志

<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>

Febrile seizure, but not hyperthermia alone, induces the expression of heme oxygenase-1 in rat cortex / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Febrile seizure (FS) is the most common seizure disorders. Approximately one third of children with a febrile seizure have recurrent events. The mechanism of FS remains unclear. Heme oxygenase-1 (HO-1) is a member of the heat shock proteins family and can be induced in the brain by various stresses, including hyperthemia and seizure. This study aimed at investigating the changes of HO-1 in the cortex of rats after recurrent FS.</p><p><b>METHODS</b>FS in rats was induced ten times, once every 2 days. In a bath of warm water, developing rats were randomly divided into two groups: control group (n = 16) and warm water-treated group (n = 50). The latter group was subdivided into hyperthermia group (n = 19) and FS group (n = 23). The expression and content of HO-1 mRNA in cortex were observed using in situ hybridization and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The content of HO-1 protein in cortex was measured using Western blotting.</p><p><b>RESULTS</b>HO-1 mRNA expression of cortex neurons in FS group was markedly increased in comparison with those in hyperthermia and control groups (P = 0.00), however, there was no statistic difference between hyperthermia group and control group (P = 0.16). The relative amount of HO-1 mRNA in cortex in FS group was increased by 53.13% and 96% in comparison with those in hyperthermia group and control group respectively (P = 0.00), but there was no obvious difference between the later two groups (P = 0.051). Western blotting analysis showed that the HO-1 protein content in cortex in FS group was increased by 198% and 246% in comparison with those in hyperthermia group and control group respectively (P = 0.00). There was no obvious difference in HO-1 protein content between the later two groups (P = 0.09).</p><p><b>CONCLUSIONS</b>Recurrent FS in rats can cause the increase of HO-1 mRNA and protein in cortex which may be involved in the mechanism of FS. The short-time recurrent hyperthermia can not induce the increase of HO-1 mRNA and protein.</p>

Gamma-aminobutyric acid B receptor regulates the expression of hydrogen sulfide/cystathionine-beta-synthase system in recurrent febrile seizures / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Febrile seizure (FS) is one of the most common seizure types in children. Our previous studies have demonstrated that both gamma-aminobutyric acid B receptor (GABABR) and hydrogen sulfide (H2S) are involved in the pathogenesis of FS. This study was designed to explore the effect of GABABR on H2S/cystathionine-beta-synthase (CBS) system in recurrent FS.</p><p><b>METHODS</b>Sixty-four Sprague-Dawley rats aged 21 days were randomly assigned into four groups: Control (37 degrees C water bath exposure), FS, FS+baclofen (GABABR excitomotor), and FS+phaclofen (GABABR inhibitor) groups (n=16 each). FS was induced by warm water bath exposure (45.2 degrees C, once every 2 days, 10 times in total. The plasma level of H2S was detected by the spectrophotometer. The expression of CBS mRNA was examined by in situ hybridization. The expressions of CBS protein was observed by immunohistochemistry.</p><p><b>RESULTS</b>The plasma level of H2S increased in the FS+baclofen group (427.45 +/- 15.91 micromol/L) but decreased in the FS+phaclofen group (189.72 +/- 21.53 micromol/L) compared with that in the FS group (362.14 +/- 19.71 micromol/L). The expressions of CBS mRNA and protein were up-regulated in the FS+baclofen group but were down-regulated in the FS+phaclofen group compared with those in the FS group.</p><p><b>CONCLUSIONS</b>GABABR modulated the expression of H2S/CBS system in recurrent FS.</p>

Effect of carbon monoxide and nitric oxide on the apoptosis of hippocampal neurons in rats with febrile seizures / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Febrile seizure (FS) is the most common type of seizure disorders in children. Recurrent FS can cause hippocampal neurons injury. At the same time heme oxygenase/carbon monoxide (HO/CO) system and nitric oxide synthase/nitric oxide (NOS/NO) system were up-regulated and interacted each other. This study examined the effects of the two systems on the apoptosis of hippocampal neurons in rats with recurrent FS.</p><p><b>METHODS</b>FS was induced in rats by exposure to warm water bath (45.2 degrees C), once every 2 days, 10 times in all. Sprague-Dawley (SD) rats aged 21 days were randomly assigned into four groups: Control (37 degrees C water bath exposure), FS, FS + ZnPP-IX (HO inhibitor) and FS + L-NAME (NOS inhibitor) groups. The apoptosis of hippocampal CA1 neurons was detected by TUNEL.</p><p><b>RESULTS</b>After recurrent FS, the apoptotic cells in the hippocampal CA1 neurons increased by 225% compared with those in the Control group (P < 0.01). The apoptotic cells in the FS+ZnPP-IX group increased by 62% and 425% compared with those in the FS and the Control groups (both P < 0.01). The apoptotic cells in the FS + L-NAME group decreased by 38% compared with those in the FS group (P < 0.01) and increased by 100% compared with those in the Control group (P < 0.05).</p><p><b>CONCLUSIONS</b>In recurrent FS, exogenous administration of HO inhibitor ZnPP-IX may induce an increase of apoptotic cells in hippocampal neurons, while NOS inhibitor L-NAME may decrease the apoptotic cells. The results suggest that the HO/CO system might alleviate neuronal damage, while NOS/NO system might augment neuronal damage.</p>

Long-term alteration of gamma-aminobutyric acid B receptor subunits in immature rats after recurrent febrile seizures / 中华儿科杂志

<p><b>OBJECTIVE</b>Febrile seizure (FS) is closely related to an altered transmission of gamma-aminobutyric acid (GABA). GABA exerts its effects through ionotropic receptors (GABA(AR) and GABA(CR)) and metabotropic receptors (GABA(BR)). GABA(BRs) are located at pre- and postsynaptic sites. Stimulation of postsynaptic receptors generates long-lasting inhibitory postsynaptic potentials (IPSPs) that are important for the fine-tuning of inhibitory neurotransmission and caused by an increase in K(+) conductance. At presynaptic sites, GABA(BRs) mediate a suppression on the release of neurotransmitters such as of GABA or glutamate by inhibiting voltage-sensitive Ca(2+) channels. The present study aimed to explore the long-term changes of GABA(B) receptor subunits in immature rats after recurrent febrile seizures.</p><p><b>METHODS</b>Rats were randomly divided into control group and hyperthermia treatment group. The control rats (n = 64) were put into 37 degrees C water for 5 minutes. Rats with hyperthermia treatment were put into 44.8 degrees C water for 5 minutes. If a rat in hyperthermia treatment group showed seizure within 5 min, the rat was taken out of the water as soon as the seizure occurred. Water-immersion was carried out 10 times, once every 2 days. Rats showing 10 seizures (FS(10), n = 64) were studied. Rats exposed to hyperthermia for 10 times without seizure were also studied as hyperthermia-only (H, n = 64) group. Rats showing one seizure at the last time of 10 times of hyperthermia treatment were studied as one-seizure group (FS(1), n = 64). The other rats were studied for other research. The changes of GABA(B)R(1) and GABA(B)R(2) co-localization were detected by double fluorescence;the quantitative alteration of GABA(B)R(1) and GABA(B)R(2) were detected by quantitative RT-PCR; the binding of GABA(B)R(2) to GABA(B)R(1) was detected by immunoprecipitation/Western blot.</p><p><b>RESULTS</b>GABA(B)R(1), GABA(B)R(2), and the binding of GABA(B)R(2) to GABA(B)R(1) decreased after the last febrile seizure in FS(10) group, the expression of GABA(B)R(1) returned to normal in later phase while GABA(B)R(2) and the binding of them did not.</p><p><b>CONCLUSION</b>Recurrent FS down-regulated the expression of GABA(B)R subunits in a long term.</p>

Effect of endogenous heme oxygenase-carbon monoxide on brain damage induced by recurrent febrile seizures / 中华儿科杂志

<p><b>OBJECTIVE</b>Febrile seizures (FS) are the most common seizure disorders in children. Approximately one third of children with a febrile seizure have recurrent events. Although most FS may not represent a serious health problem, those that are more prolonged and recurrent may cause hippocampal damage which is the most important pathological basis of temporal lobe epilepsy. The present study aimed to explore the effect of endogenous heme oxygenase (HO)-carbon monoxide (CO) system on brain damage induced by recurrent FS.</p><p><b>METHOD</b>Twenty-four Sprague-Dawley rats aged 21 days were randomly divided into three groups: Control group (immersed in 37.0 degrees C water, n = 8), FS group (immersed in 45.2 degrees C water, n = 8), FS + zinc protoporphyrin (ZnPPIX) group (immersed in 45.2 degrees C water, n = 8). FS in rats were induced ten times in a bath of warm water, once every 2 days. The indirect production of CO in plasma was detected by a dual wavelengh spectrophotometer. The intensity, latency, duration and rectal temperature of the seizure in rats were recorded. Morphologic changes of hippocampal neurons were observed with HE staining. The ultrastructural changes of the hippocampal neurons were observed under electron microscope. Semiquantitative analysis of hippocampal neurons was carried out by using Nissl stain.</p><p><b>RESULT</b>After recurrent FS, the content of CO in plasma in FS group was increased as compared with that in control group (P < 0.01). The content of CO in plasma in FS + ZnPPIX group was decreased as compared with that in FS group (P < 0.01), while no significant difference in CO content was found as compared with that in control group (P > 0.05). In FS group, with the increase of seizure number, there was a trend of gradual prolongation of the seizure duration. In FS + ZnPPIX group, the seizure latency was gradually shortened and the seizure duration was further prolonged. There were no significant differences in seizure intensity and rectal temperature between the two groups. After recurrent FS, by using light microscope we could see that the arrangement of hippocampal neurons was disordered, polarity was not clear and vacuolization appeared in some neurons. At the same time the ultrastructure of hippocampal neurons under electron microscope changed, which manifested as mitochondrial swelling, dissolved and ruptured ridge and vacuole formation, and dilated rough endoplasmic reticulum (RER). ZnPPIX aggravated neuronal injury. No obvious loss of hippocampal neurons was observed in FS group, while the number of hippocampal neurons in CA(1) and CA(3) subfields in FS + ZnPPIX group decreased respectively as compared with that in FS group and in control group (P < 0.01 for all).</p><p><b>CONCLUSION</b>The study by using ZnPPIX which is an inhibitor of HO showed that endogenous HO/CO might act as a protective factor in FS-induced brain damage.</p>