Clinical features of benign epilepsy of childhood with centrotemporal spikes in chinese children.

This multicenter clinical trial was conducted to examine current practice of benign epilepsy with centrotemporal spikes and especially address the question that in what circumstances 1 antiepileptic drug (AED) should be preferred.Twenty-five medical centers participate in this clinical trial. The general information, clinical information, and treatment status were collected under the guidance of clinicians and then analyzed. Difference between different treatment groups was compared, and usefulness of the most commonly used AEDs was evaluated.A total of 1817 subjects were collected. The average age of the subject was 8.81 years. The average age of onset is 6.85 years (1-14 years). Male-to-female ratio is 1.13:1. A total of 62.9% of the patients are receiving monotherapies, and 10.6% are receiving multidrug therapy. Both age and course of disease of treated rolandic epilepsy (RE) patients are significantly different from those of untreated patients. Bilateral findings on electroencephalography (EEG) are less seen in patients with monotherapy compared with patients with multidrug therapy. Except for 25.4% patients not taking any AEDs, oxcarbazepine (OXC), sodium valproate (VPA), and levetiracetam (LEV) are the most commonly used 3 AEDs. VPA and LEV are commonly used in add-on therapy. OXC and LEV are more effective as monotherapy than VPA.Age of onset of Chinese RE patients is 6.85 years. Bilateral findings on EEG could be a risk factor to require multidrug therapy. In Chinese patients, OXC, VPA, and LEV are most commonly used AEDs as monotherapy and OXC and LEV are more effective than VPA.

Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress.

Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons. Interestingly, we found VP1-activated endoplasmic reticulum (ER) stress and autophagy could promote Ecto-CRT upregulation, but ER stress or autophagy alone was not sufficient to induce CRT exposure. Furthermore, we demonstrated that VP1-induced autophagy activation was mediated by ER stress. Meaningfully, we found dexamethasone treatment could attenuate Ecto-CRT upregulation by alleviating VP1-induced ER stress. Altogether, these findings identify VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications.

Reversible splenial lesion syndrome in children: Retrospective study and summary of case series.

OBJECTIVE: To describe clinical features of reversible splenial lesion syndrome (RESLES) in children. METHODS: Retrospectively analyzed clinical features of RESLES in children and compared differences between severe and non-severe group, classified by clinical global impression-scale; summarized clinical features of children with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) from case series. RESULTS: 16 episodes of RESLES occurring in 15 Chinese children were analyzed, with 13 episodes having MERS and 3 episodes with epilepsy. 10 episodes were associated with various pathogens including rotavirus (n=5), adenovirus (n=1), influenza A (n=1), mycoplasma (n=2), and jejunum campylobacter (n=1). The common neurological symptoms included seizure, behavioral changes, altered consciousness and motor deterioration. The lesions of splenium of corpus callosum (SCC), extra-SCC (n=2) or extra-CC (n=1) showed T2-weight and FLAIR hyper-intensity, with the corresponding reduced diffusion. All had complete resolution of radiological changes except 1 episode with small residual. 8 episodes had EEG abnormalities, while elevated white blood count, increased hs-CRP, and hyponatremia were commonly revealed. 7 episodes were given steroid plus therapy, while 3 episodes were treated with antiepileptic drugs. Compared with non-severe group, the number of patients with altered consciousness, EEG abnormalities, motor deterioration, or extra-SCC lesions in severe group was significantly increased. The patients in severe group tended to need longer hospital stay interval. No case caused neurological sequelae, except 1 patient in severe group with recurrent episode and extra-CC lesions having intellectual disability (ID). Five pediatric MERS case series were summarized, including 67 episodes (40 male and 27 female; age ranging 10 m∼13y) from 65 patients, with 33 episodes in Japan, 27 in China, and 7 in Caucasian Australian children, and all patients have a good prognosis except 1 patient with ID (current study). CONCLUSION: Although RESLES in children tend to be a good outcome, the prognosis of patient in severe group, especially with extra-CC lesions, might have neurological sequelae.

[Evolution and prognosis of the acute flaccid paralysis associated with enterovirus 71 infection evaluated through a clinical and magnetic resonance imaging follow-up study].

OBJECTIVE: To explore the development and prognosis of the acute flaccid paralysis (AFP) associated with enterovirus 71 (EV71) infection through clinical follow-up study for clinical and magnetic resonance imaging (MRI) features based on the research progress of virology and pathology. METHOD: Sixteen children with HFMD associated with AFP in hospital from May 1, 2011 to August 31, 2011 were investigated and the patients received intensive rehabilitation training. The 16 cases were divided into two groups (the recovery or the sequela) by if the muscle strength recovered to level 4 after intensive rehabilitation. The MRI findings of 15 children were analyzed and among them, 6 patients were reexamined after one month. The clinical markers were compared between groups including course of disease, WBC, WBC in cerebrospinal fluid (CSF), ventilator support, therapy, the worst muscle strength, the initial tendon reflex, the muscle atrophy, and multi-limb paralysis. The data were analyzed by t test and χ2 test with SPSS10.0. RESULT: All the 16 children were infected with enterovirus 71 (EV71). The myodynamia of 7 children were level 0, 4 children had serious upper limbs paralysis. The neck muscle in 3 cases and the brain stem motor ruckus in 4 cases were involved. The ankle clonus of non-completely paralyzed limbs in 14 cases occurred during rehabilitation. Eight children had the better prognosis, the other 8 children had sequela. 0 level muscle strength (0 case vs. 7 cases, χ2=12.4), the initial tendon reflex (2 cases vs. 8 cases, χ2=9.6), obvious muscle atrophy (0 case vs. 8 cases, χ2=16), were significantly different in the children with the recovery when compared to the sequela (P<0.01). The severe upper limbs paralysis had the worse prognosis than the severe lower limbs paralysis. MR imaging showed signs of spinal nerve root inflammation and the bilateral hyperintense lesions, symmetrical in the posterior portions of the medulla, pons, and asymmetrical in the ventral horns of cervical spinal cord. Signal enhancement occurred only in the early MRI examination. CONCLUSION: In the evolution of AFP due to EV71 infection, the upper motor neuron damage is common, the prognosis is related with the severity of early paralysis and neuron damage. MR imaging is helpful to understand the pathological mechanism of AFP.

Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting. METHODS: This 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent-rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures. RESULTS: A total of 1447 children with ADHD (mean age (9.52 ± 2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P < 0.001) improvement with OROS-MPH (mean: 6.95 ± 2.71) versus the score at baseline (10.45 ± 2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study. CONCLUSION: This open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice.

[Interictal epileptiform discharges in children with epilepsy].

OBJECTIVE: To study the features of interictal epileptiform discharges (IED) during sleep and wakefulness in children with epilepsy. METHODS: The polysomnography, active EEG and video EEG were performed on 48 children with epilepsy during the whole night, and wakefulness of pre- and post-sleep. The epileptiform sharp/spike discharge indexes during sleep and wakefulness were recorded. The positive rate of IED in focal and generalized epilepsy was compared. RESULTS: Of the 48 patients, 25 showed IED, including 9 cases (36.0%) in the generalized seizure group and 16 cases (64.0%) in the focal seizure group (P<0.05). The epileptiform sharp/spike discharge indexes in the whole non-rapid eye movement (NREM) sleep stage (stages S1-S4: 21.13+/-19.96, 19.59+/-17.76, 22.85+/-18.99, and 20.37+/-16.63) were significantly higher than that in the wakefulness stage (8.20+/-6.21) (P<0.05). The discharge index in the S3 stage during NREM sleep was higher than that during the rapid eye movement (REM) sleep (22.85+/-18.99 vs 12.91+/-10.95; P<0.05). CONCLUSIONS: The positive rate of IED in the focal seizure group was higher than that in the generalized seizure group. Sleep, especially NREM sleep, facilitates IED in children with epilepsy.

[Effects of transcutaneous electrical nerve stimulation on motor function in ambulant children with spastic cerebral palsy: a randomized trial].

OBJECTIVE: To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on motor function in children with spastic cerebral palsy (CP). METHODS: After signing the informed consent, 78 children with CP, aged 45.6 +/- 8.5 months (36 to 58 months), were randomly divided into a TENS group (n = 40) and a control group (n = 38). All the subjects received standardized functional exercise program. In TENS group, 2 TENS devices were used and the surface electrodes were applied on the spastic musculotendinous and antagonist muscles in the affected lower extremity. TENS lasted for 20 min per session, 5 days weekly for 6 weeks. After 6 weeks, the functional exercise program was applied by the caregivers. Demographic data were recorded, including age, gender, number of the hemiplegic and diplegic CP, level of gross motor function classification system (GMFCS). Clinical assessments included the composite spasticity scale (CSS), D and E dimensions of the Gross Motor Function Measure (GMFM), and walking velocity was determined before treatment and at 6, 12 and 24 weeks after treatment. RESULTS: No statistically significant differences were found in age, gender, number of the hemiplegic and diplegic CP, level of GMFCS, as well as clinical assessments (CSS, GMFM and walking velocity) before treatment between the 2 groups (P > 0.05). All the children showed a reduction of spasticity (CSS) after 6, 12 and 24 weeks of treatment (P < 0.05). When compared with the results obtained before treatment, the improvement of standing and walking (GMFM), walking velocity was statistically significant after 6, 12 and 24 weeks of treatment (P < 0.05). Furthermore, the differences of CSS, GMFM and walking velocity between the two groups at 6, 12 and 24 weeks examination were also statistically significant (after 24 weeks of treatment: t value was 8.96, 3.14 and 2.35, P < 0.05, respectively). CONCLUSION: When compared with the control group, 6 weeks of TENS treatment on the affected lower extremity was more effective in terms of reducing spasticity and improving functional performance in standing, walking, and walking velocity in ambulant children with the spastic CP.

[Overnight sleep structure of children with epilepsia].

OBJECTIVE: To evaluate the effect of epilepsy on sleep in children. METHODS: Whole night polysomnography was performed in 48 epileptic children and 12 healthy controls. The 48 epileptic children were divided into focal seizure and generalized seizure groups and into waking seizure and sleeping seizure groups according to the time of occurrence of the seizures. Various parameters of sleep structure were analyzed. RESULTS: The sleep efficiency of epileptic children was significantly lower than that of the healthy controls (85.4 +/- 8.6% vs 90.9 +/- 5.8%; P < 0.05). The total recording time (TRT) of sleep was significantly longer and the sleep efficiency was significantly lower in the focal seizure group compared to the control group (P < 0.05). The percentage of stage 1 non-rapid-eye-movement sleep (S1 sleep) increased and the percentage of rapid-eye-movement (REM) sleep decreased in the generalized seizure group compared to the control group (P < 0.05). The percentage of S1 sleep increased and both the percentage of REM sleep and the sleep efficiency decreased in the sleeping seizure group as compared with the control group (P < 0.05). There were no significant differences in the parameters of sleep structure between the waking seizure and the control group. Among the sleeping seizure group, the children with generalized seizure showed significantly lower REM sleep percentage and sleep efficiency, and those with focal seizure had significantly longer TRT and higher S1 sleep percentage as compared with the controls. CONCLUSIONS: Epilepsy affects sleep structure of patients, and different types of seizure have different influences on sleep structure. Children with generalized seizure have prolonged light sleep and shortened REM sleep. When generalized seizures occur during waking, the increase of light sleep is more pronounced. While generalized seizures occur during sleeping, REM sleep reduction is more prominent. Children with focal seizures have decreased sleep efficiency. When focal seizures occur during waking, the sleep structure of patients is normal. However, when seizures occur during sleeping light sleep increases and sleep efficiency decreases.

[Effects of botulinum toxin guided by electric stimulation on spasticity in ankle plantar flexor of children with cerebral palsy: a randomized trial].

OBJECTIVE: To compare the effects of botulinum toxin A (BTX-A) injection guided by electric stimulation combined with physiotherapy, with physiotherapy only on the spasticity of the ankle plantar flexor in children with cerebral palsy (CP). METHODS: After signing the informed consent, 43 children with CP, aged 52.4 +/- 13.2 months (35 to 82 months), were randomly assigned into 2 groups, (1) BTX-A group (n = 23) treated with BTX-A injection guided by electric stimulation and (2) physiotherapy alone group (n = 20). Children in BTX-A group received injection of HengLi BTX-A in the ankle plantar flexors. A maximum dose of 12 units of BTX-A per kilogram body weight and maximumly 10 units of BTX-A per site were administered. Localization technique was the use of electrical stimulation guidance. Physiotherapy and ankle-foot orthosis were applied to children at 72 hours after injection in BTX-A group and at the time of being recruited into physiotherapy group. Ten days after entering into the study, the program was applied by the parents. Demographic data, including age, gender, number of the spastic lower limbs, affected side (left or right) were recorded. Clinical assessments included the range of passive movement (PROM) measured by goniometer while children maintained the knee extended, modified Ashworth scale (MAS), composite spasticity scale (CSS), D and E dimensions of the Gross Motor Function Measure (GMFM), and walking velocity (WV) was determined before treatment and at 2 weeks, 1, 2, and 3 months after treatment. RESULTS: No statistically significant differences were found in age, gender, number of the spastic lower limbs, affected side, as well as clinical assessments (PROM, MAS, CSS, GMFM and WV) before treatment between the 2 groups (P > 0.05). All the children showed a reduction of spasticity (PROM, MAS and CSS) after 2 weeks, 1, 2, and 3 months of treatment (P < 0.05). When compared with the baseline findings, the improvement of standing and walking (GMFM), walking velocity were statistically significant after 2 weeks, 1, 2, and 3 months of treatment (P < 0.05). Furthermore, the differences of PROM, MAS and CSS between the 2 groups at 2 weeks, 1, 2, and 3 months examination were also statistically significant (after 3 months of treatment: t(PROM) = 6.48, t(MAS) = 9.74, t(CSS) = 9.59; P < 0.05). The difference in GMFM between the 2 groups was statistically significant (t(1M) = 2.20, t(2M) = 3.26, t(3M) = 4.13; P < 0.05) at 1, 2, and 3 months after treatment. The difference of WV between the 2 groups was statistically significant (t(2M) = 2.12, t(3M) = 2.57; P < 0.05) at 2 and 3 months after treatment. CONCLUSION: BTX-A injection guided by electrical stimulation in combination with physiotherapy was more effective than physiotherapy alone in terms of reducing spasticity and improving functional performance in standing, walking, walking pattern and velocity on spasticity in ankle plantar flexors of ambulant children with CP.

[Analyze of the clinical characteristics in children with the severe abnormal auditory brainstem response and normal distortion product otoacoustic emission].

OBJECTIVE: To explore the clinic and audiological characteristics of auditory neuropathy in children. METHODS: Between 2002 and 2004, ninety-eight cases with the severe abnormal results of ABR and the normal results of DPOAE were enrolled in the study group. The mean patient age was 9 months, with a range of 1 month to 5 years. According to the evaluation of pediatric neurologist, the high-risk factors of psychomotor development retardation were statistically analyzed whether the cases were accompanied by psychomotor development retardation or not. The cases with abnormal results of ABR and DPOAE and without abnormal conductive function were selected as the cochlea lesion group. Some same age children without hearing loss were subjected as normal control group. RESULTS: The psychomotor development retardation was performed in 83.67% of cases. Hypercholesterolemia of newborn was the common high-risk factor of psychomotor development retardation (43.88% ). Severe abnormal results of ABR were occurred in 66. 07% of ears. Prolonged latency of wave I - V ABR and acoustic stapedius reflex were observed in few cases. The DPOAE amplitudes at intermediate and high frequencies were normal or slightly descending. Occurring rate of DPOAE at intermediate and high frequencies was the same as in normal control group. CONCLUSIONS: Hypercholesterolemia of newborn is the most common cause of auditory neuropathy. The auditory test results are various in children with auditory neuropathy. This character is different from it in adults.