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5% CO2 inhalation suppresses hyperventilation-induced absence seizures in children

Hyperventilation can cause respiratory alkalosis by exhaling CO2, and is often used to confirm diagnosis of absence epilepsy. CO2 has long been known for its anticonvulsant properties since the 1920s. In this pilot study, we aimed to determine whether inhaling medical carbogen containing 5% CO2 and 95% O2 can suppress hyperventilation-induced absence seizures and spike-and-wave discharges (SWDs). We examined 12 patients whose absence seizures were induced by hyperventilation using video electroencephalographic recording for at least 4h. The patients were asked to hyperventilate for 3 min while breathing the following gases: (1) room air (12 patients); (2) carbogen (12 patients); and (3) 100% O2 (8 patients). Eight out of twelve patients were also examined in room air through pretreatment with carbogen for 3 min before the 3 min hyperventilation. Compared with hyperventilation in room air, hyperventilation supplemented with 5% CO2 had the following effects: (a) decrease in the number and duration of seizures; (b) prolonged appearance of epileptic discharges; and (c) reduction in the number and duration of SWDs (P<0.001). However, pretreatment with 5% CO2 and 100% O2 supplement did not yield similar effects. We demonstrated that 5% CO2 could suppress hyperventilation-induced absence seizures and SWDs, supporting the claim that 5% CO2 is an effective anticonvulsant agent. Our pilot study provides clinical basis that 5% CO2 inhalation could be a therapeutic approach for hyperventilation-related seizures.

Two compound frame-shift mutations in succinate dehydrogenase gene of a Chinese boy with encephalopathy

OBJECTIVE To investigate respiratory chain complex II deficiency resulted from mutation in succinate dehydrogenase gene (SDH) encoding complex II subunits in China. METHODS An 11-year-old boy was admitted to our hospital. He had a history of progressive psychomotor regression and weakness since the age of 4years. His cranial magnetic resonance imaging revealed focal, bilaterally symmetrical lesions in the basal ganglia and thalamus, indicating mitochondrial encephalopathy. The activities of mitochondrial respiratory chain enzymes I-V in peripheral leukocytes were determined via spectrophotometry. Mitochondrial DNA and the succinate dehydrogenase A (SDHA) gene were analyzed by direct sequencing. RESULTS Complex II activity in the leukocytes had decreased to 33.07nmol/min/mg mitochondrial protein (normal control 71.8±12.9); the activities of complexes I, III, IV and V were normal. The entire sequence of the mitochondrial DNA was normal. The SDHA gene showed two heterozygous frame-shift mutations: c.G117G/del in exon 2 and c.T220T/insT in exon 3, which resulted in stop codons at residues 56 and 81, respectively. CONCLUSIONS We have described the first Chinese case of mitochondrial respiratory chain complex II deficiency, which was diagnosed using enzyme assays and gene analysis. Two novel, compound, frame-shift mutations, c.G117G/del in exon 2 and c.T220T/insT in exon 3 of the SDHA gene, were found in our patient.

Efficacy and safety of a mammalian target of rapamycin inhibitor in pediatric patients with tuberous sclerosis complex: A systematic review and meta‑analysis

Inhibitors of mammalian target of rapamycin (mTOR) are increasingly used as therapy for pediatric patients with tuberous sclerosis complex (TSC). The uncertainty over the efficacy and safety of mTOR inhibitor therapy for the treatment of pediatric patients with TSC emphasizes the necessity for a synthesis of existing evidence. The aim of this study was to assess the efficacy and safety of mTOR inhibitor therapy for the treatment of pediatric patients with TSC. The PubMed, EmBase and Cochrane Library electronic databases were searched, and studies of mTOR inhibitor therapy and non-mTOR inhibitor therapy in pediatric patients with TSC (<18 years old) were selected. Eleven studies met the inclusion criteria. There was evidence of a significantly increased response rate in pediatric patients with TSC treated with mTOR inhibitor therapy compared with those treated with non-mTOR inhibitor therapy (odds ratio, 24.71; 95% confidence interval, 7.46–81.72; P<0.001). The majority of studies reported few adverse events. There was an increased incidence of mouth ulceration, stomatitis, convulsion and pyrexia in pediatric patients with TSC treated with mTOR inhibitor therapy. In conclusion, mTOR inhibitor therapy is an efficacious and safe treatment for pediatric patients with TSC.

Febrile seizure recurrence reduced by intermittent oral levetiracetam

Febrile seizure (FS) is the most common form of childhood seizure disorders. FS is perhaps one of the most frequent causes of admittance to pediatric emergency wards worldwide. We aimed to identify a new, safe, and effective therapy for preventing FS recurrence.

Development of a mouse model of infantile spasms induced by N-methyl-d-aspartate

Using N-methyl-D-aspartate (NMDA) injection, we attempt to develop a mouse model for infantile spasms (IS). Experiments were performed in postnatal 11- to 13-day-old C57 and Balbc mice. In the pilot experiment, mice were injected with different doses of NMDA (7, 15, and 30 mg/kg) to determine the optimal age and convulsant doses of NMDA. In further experiment optimal age mice were divided into five groups: group A, control group that received intraperitoneal injection of physiological saline; group B, convulsion group that was given intraperitoneal NMDA; group C, pretreatment group that received adrenocorticotropin (ACTH) injection (100 IU/kg) 30 min before NMDA administration; group D, electroencephalogram (EEG) group that received EEG recording, group E, performance group that received motor and learning test at different time point after NMDA administration. The behaviors of each group were observed continuously for 3h, the latency and the total numbers of spasms were recorded. Pilot experiments showed that a 15 mg/kg dose of NMDA could induce typical spasm-like seizures in P13 C57 mice, NMDA administration caused anxiety and deficits in motor and cognitive functions at early time and that large doses of ACTH reduced the number of seizures and rating scale (P<0.05). The NMDA mouse model has the following characteristics: age dependency, spasm-like seizures, cognitive impairment and response to ACTH, which fulfills the criteria of an IS model.

Detection of global DNA hypomethylation of peripheral blood lymphocytes in patients with infantile spasms.

The pathogenesis of infantile spasms remains unclear. DNA methylation may play a pivotal role in the development of some types of neurological diseases, such as epilepsy. In this study, we aimed to investigate the relationship between global DNA methylation of peripheral blood leukocytes and cryptogenic infantile spasms. DNA from peripheral blood leukocytes was extracted from 20 patients with cryptogenic infantile spasms and 20 gender and age matched healthy controls. Global DNA methylation percentage of peripheral blood leukocytes was measured using a global DNA methylation quantification kit. Global DNA methylation levels of peripheral blood lymphocytes in patients with cryptogenic infantile spasms (23.4 ± 20.0%) were significantly lower than those in healthy controls (46.8 ± 8.4%). Furthermore, we did not find any association between the levels of DNA methylation and effectiveness of Adrenocorticotropic hormone treatment. Our study demonstrates that global DNA hypomethylation of peripheral blood lymphocytes is correlated with infantile spasms. This finding provides information for better understanding of the pathogenesis of infantile spasms.

Increased precipitation of spasms in an animal model of infantile spasms by prenatal stress exposure.

Infantile spasms (IS) represent a serious epileptic syndrome, called West syndrome (WS) that occurs in the early infantile age. Although several hypotheses and animal models have been proposed to explain the pathogenesis of IS, the pathophysiology of IS has not been elucidated. Recently, we proposed a hypothesis for IS under prenatal stress exposure (also called Zous hypothesis) by correlating diverse etiologies and prenatal stresses with IS development. This research aims to determine the mechanism through which prenatal stress affects the offspring and establish the potential underlying mechanisms. Pregnant rats were subjected to forced swimming in cold water. Rat pups exposed to prenatal stress were administered with N-methyl-D-aspartate (NMDA). Exposure to prenatal stress sensitized the rats against development of NMDA-induced spasms. However, this phenomenon was altered by administering adrenocorticotropin. Prenatal stress exposure also altered the hormonal levels and neurotransmitter receptor expression of the developing rats as well as influenced the tissue structure of the brain. These findings suggest that maternal stress could alter the level of endogenous glucocorticoid, which is the basis of IS, and cerebral dysplasia, hypoxic-ischemic encephalopathy (HIE), inherited metabolic diseases, and other factors activated this disease in developmental brain.

A novel iduronate 2-sulfatase mutation in a Chinese family with mucopolysaccharidosis type II

BackgroundMucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is an X-linked multisystem disorder resulting from the defective activity of the enzyme iduronate-2-sulfatase (IDS). Genetic testing is crucial in clarifying and diagnosing different types of MPS diseases. In this paper we report a novel IDS nonsense mutation resulting in MPS II in several patients from a Chinese family.MethodsIDS enzyme activity, polymerase chain reaction, and DNA sequencing were performed to confirm the diagnosis of MPS II.ResultsThree patients had no detectable IDS activity. Two genetic tests revealed a novel IDS nonsense mutation (c.1030G>T, p.E344X) inherited from their mothers. The nonsense mutation shortened the peptide chain from 550 to 344 amino acids, which is believed to be a disease-causing mutation.ConclusionsMPS II is inherited in an X-linked manner. The risk to sibs depends on the carrier status of the mother. Genetic testing is necessary to identify disease-causing mutation. With this information, carrier testing for at-risk female relatives and prenatal testing for pregnancies at increased risk become possible.