Vigabatrin pediatric dosing information for refractory complex partial seizures: Results from a population dose–response analysis

We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose–response model related seizure‐count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure‐count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10–15 and >15–20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10–15 and >15–20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25–60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25–60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg.     

Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD95-MLK3 signaling module

Our previous study showed that when glutamate receptor （GluR）6 C terminus-containing peptide conjugated with the human immunodeficiency virus Tat protein （GluR6）-9c is delivered into hippocampal neurons in a brain ischemic model, the activation of mixed lineage kinase 3 （MLK3） and c-Jun NH2-terminal kinase （JNK） is inhibited via GluR6-postsynaptic density protein 95 （PSD95）. In the present study, we investigated whether the recombinant adenovirus （Ad） carrying GluR6c could suppress the assembly of the GluR6-PSD95-MLK3 signaling module and decrease neuronal cell death induced by kainate in hippocampal CA1 subregion. A seizure model in Sprague-Dawley rats was induced by intraperitoneal injections of kainate. The effect of Ad- Glur6-9c on the phosphorylation of INK, MLK3 and mitogen-activated ldnase kinase 7 （MKK7） was observed with western immunoblots and immunohistochemistry. Our findings revealed that overexpression of GluR6c inhibited the interaction of GluR6 with PSD95 and prevented the kainate-induced activation of INK, MLK3 and MKK7. Furthermore, kainate-mediated neuronal cell death was significantly suppressed by GluR6c. Taken together, GluR6 may play a pivotal role in neuronal cell death.     

合并癫痫的病人心跳骤停复苏后亚低温治疗对预后的影响

目的：评价癫痫病人对于心跳骤停复苏后接受亚低温治疗对预后的影响。方法：回顾首都医科大学大兴医院重症医学科于2012年1月～2014年1月收治的心脏骤停复苏成功后给予亚低温治疗并进行连续脑电监测的成年患者42例。其中男性22例（52％）,女性20例（48％）,年龄31～62岁,平均47岁。既往有癫痫病史的4例（10％）。通过医院电子病历信息系统查阅病历资料收集所需数据信息。结果：在纳入的42例患者中,有15例（36％,95％置信区间为21％～50％）发生了癫痫,其中7例（17％）发生在亚低温治疗过程中;34例（81％）死亡,其中26例死于医院内,8例存活出院但仍在心脏骤停发生后的28d内死亡。15例发生癫痫的患者均死亡,其中13例（87％）死于院内,2例（13％）存活出院但28d内死亡;未发生癫痫的27例患者中有11例（41％）死亡,16例（59％）存活超过28d。发生癫痫组的患者死亡率显著高于未发生癫痫者（P〈0．001）。结论：提示有癫痫发作症状的患者心肺复苏后接受亚低温治疗预后不良。应用连续脑电监测技术可能有利于早期发现癫痫并采取有效的措施改善患者预后。     

Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures

Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological state such as complex febrile seizures（FSs） in infancy. Here we used a well-established complex FS model in rats and showed that：（1） the susceptibility to seizures induced by hyperthermia, pentylenetetrazol（PTZ）, and maximal electroshock（MES） was similar in male and female rat pups, while males were more susceptible to PTZ- and MES-induced seizures than age-matched females in normal adult rats;（2） adult rats with complex FSs in infancy acquired higher seizure susceptibility than normal rats; importantly, female FS rats were more susceptible to PTZ and MES than male FS rats; and（3） the protein expression of interleukin-1β, an infl ammatory factor associated with seizure susceptibility, was higher in adult FS females than in males, which may reflect a gender-difference phenomenon of seizure susceptibility. Our results provide direct evidence that the acquired seizure susceptibility after complex FSs is gender-dependent.     

Occipital seizures induced by Intermittent Photic Stimulation in Dravet syndrome

PurposeDravet syndrome (DS) is a rare disorder with seizure onset in the first year of life, typically beginning with prolonged febrile hemiclonic seizures or generalized tonic–clonic seizures. Photosensitivity is reported in more than 40% of patients. We present two cases of DS in which we had the chance to record occipital seizures induced by Intermittent Photic Stimulation (IPS).MethodWe retrospectively reviewed the medical records of 32 children affected by DS. All clinical notes were reviewed in order to evaluate the occurrence of seizures induced by IPS.ResultsAmong the 32 reviewed clinical records, two patients with IPS-induced seizures were found. In both patients seizures originated from the occipital-temporal region. Clinical history was characterized by generalized tonic–clonic seizures, and myoclonia. At the age respectively of 11 months and 20 months they presented a prolonged focal seizure induced by IPS at a frequency of 10 Hz. During the follow-up they additionally presented with hypomotor seizures, also induced by IPS during laboratory EEG examinations. The semiology of hypomotor seizures resembled what is described as “complex partial status”, a type of non-convulsive status with ictal discharges arising unilaterally from the occipito-temporal region.ConclusionBased on available literature, IPS induced occipital seizures have not been reported during the first year of life. Although pathophysiological features are not yet completely understood, both photosensitivity and occipital seizures should be considered in the diagnostic evaluation in DS. The documentation of IPS induced occipital seizures might contribute to widen the clinical and neurophysiological spectra of DS.     

The development of pediatric fluid resuscitation: an interview with Dr. Frederic A. ‘Fritz’ Berry

Dr. Frederic A. ‘Fritz’ Berry (1935), Professor Emeritus of Anesthesiology and Pediatrics at the University of Virginia, has played a pioneering role in the development of pediatric anesthesiology through training generations of anesthesiologists. He identifies his early advocacy of balanced electrolyte solution for perioperative fluid resuscitation as his defining contribution. Based on his clinical experiences, he pushed to extend the advances in adult fluid resuscitation into pediatric practice. He imparted these and other insights to his colleagues although textbooks, book chapters, original journal publications, and decades of Refresher Course Lectures at the American Society of Anesthesiologists' annual meetings. A model educator, clinician, and researcher, he shaped the careers of hundreds of physicians‐in‐training while advancing the field of pediatric anesthesiology.