Lin-Yan Hu

Genetic and biochemical findings in Chinese children with Leigh syndrome.

This study investigated the genetic and enzymological features of Leigh syndrome due to respiratory chain complex deficiency in Chinese patients. The clinical features of 75 patients were recorded. Mitochondrial respiratory chain enzyme activities were determined via spectrophotometry. Mitochondrial gene sequence analysis was performed in 23 patients. Five core pedigrees were investigated via restriction fragment length polymorphism and gene sequencing. Psychomotor retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%) were the most frequent manifestations. Sixty-four patients (85.3%) had isolated respiratory complex deficiencies: complex I was seen in 28 patients (37.3%); complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight point mutations were found in mitochondrial structural genes: m.4833A>G in ND2, m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA-Ala. One patient and their mother both had the m.12338T>C and m.8993T>C mutations. In conclusion, mitochondrial respiratory chain complex I deficiency and structural gene mutations frequently occur in Chinese Leigh syndrome patients.

An 8-year old boy with continuous spikes and waves during slow sleep presenting with positive onconeuronal antibodies

OBJECTIVE To determine the etiology of epilepsy with continuous spikes and waves during slow sleep (CSWS)/electrical status epilepticus during sleep (ESES) in an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus. MATERIAL & METHODS A combination of clinical characterization and follow-up, video EEG and laboratory investigations. RESULTS We report the case of an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus, who presented with intellectual disability, pharmacotherapy-resistant epilepsy and CSWS/ESES. Although the patients neuroblastoma had been successfully treated 8 years prior to presentation and an extensive workup did not show a tumor reoccurrence, testing for onconeuronal antibodies was positive for anti-Ma2 and anti-CV2/CRMP5 antibodies. High-dose intravenous methylprednisolone and a taper of oral methylprednisolone were given, leading to a significant clinical improvement. During the taper the patients condition and EEG manifestations deteriorated again necessitating another cycle of steroid therapy, which lead to a stable improvement. During a 6-month follow-up no CSWS/ESES was seen on EEG and anti-Ma2 and anti-CV2/CRMP5 antibodies remained undetectable. CONCLUSION This case suggests that onconeuronal antibodies may be involved in the pathogenesis of CSWS/ESES.

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.

Hypercapnia-induced brain acidosis: Effects and putative mechanisms on acute kainate induced seizures

Aims: This study investigated the mechanism of the anticonvulsant effects of carbogen containing 5% CO2 in a kainic acid (KA) rat model. Main methods: Four‐week‐old Sprague–Dawley rats were divided into four groups: control, carbogen, KA + air, and KA + carbogen. Carbogen containing 5% CO2 was applied immediately after KA injection, and cortical pH was recorded. High‐performance liquid chromatography was used to detect the release of &ggr;‐aminobutyric acid (GABA) and glutamate. We used electrophysiology to measure cortical and hippocampal activities. Key findings: Carbogen increased the onset latency of seizure (KA + air group, 26.12 ± 2.11 min; KA + carbogen group 43.65 ± 2.78 min, P < 0.001) and reduced the frequency of seizures (KA + air group, 12.50 ± 1.77; KA + carbogen group, 5.63 ± 1.59, P < 0.001). Carbogen inhalation could reduce cortical pH (KA + air group, 7.04 ± 0.04; KA + carbogen group, 6.82 ± 0.03, P < 0.001). After carbogen inhalation, the levels of excitatory amino acid glutamate decreased (595.90 ± 7.51 in KA + air group vs. 467.95 ± 4.82 in KA + carbogen s group, P < 0.001), whereas GABA increased significantly (158.30 ± 5.05 in KA + air group vs. 216.62 ± 5.59 in KA + carbogen, P < 0.05). Carbogen reduced both electrohippocampalogram (119.57 ± 2.83 in KA + air group vs. 107.48 ± 2.95 in KA + carbogen group, P < 0.01) and electrocorticogram (130.74 ± 2.48 in KA + air group vs. 115.35 ± 2.11 in KA + carbogen group, P < 0.01). Significance: Carbogen containing 5% CO2 decreased seizures by reducing cortical pH, by increasing GABA release, and by affecting electrical activity of the brain. HighlightsCarbogen decreased KA‐induced seizures.KA and carbogen produced a synergistic effect, further reducing cortical pH.Carbogen reduced glutamate release and increased GABA release.Carbogen reduced hippocampal and cortical activity.

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.