Prognosis of Childhood Seizure Disorders: Present and Future

Summary: The prognoses for seizure disorders have been examined since the beginnings of epileptology, and only recently has the realization emerged that, ultimately, prognosis depends on causation, which, in turn, determines whether a condition is self-limited or progressive. This factor is more important than either mode or alacrity of therapeutic intervention. The epilepsies are a series of conditions that have the final common path of either increasing cerebral irritability or synchronizing normally occurring electrical activity in such a manner that seizures result. In turn, some seizure disorders are characterized by secondary changes in neuronal synaptogenesis, leading to the development of circuits of predilection, which then render the process autonomous. Epilepto-genesis has then become epilepsy, which is the norm in acquired rather than genetic epileptogenesis. An understanding of the basic differences between the primary (idiopathic) epilepsies and the secondary (acquired or symptomatic) epilepsies is basic to a discussion concerning prognosis and to the development of a definitive individualized treatment plan. An elucidation of the genetic factors in idiopathic epilepsy and their neurochemical consequences represents a major frontier in epileptology.     

In vivo mapping of drug-induced seizures with voltage-sensitive dye

The voltage-sensitive dye diO-C2-5 was used to produce an in vivo map of the membrane potential in two types of seizures. Mild limbic seizures were induced in rats with kainic acid; clonic convulsive seizures were induced with bicuculline. Kainic acid animals showed various levels of neural depolarization during their seizures in limbic, thalamic, cortical, and brainstem sites. The bicuculline animals showed uniformly greater levels of neural depolarization during their seizures. The magnitude of these changes relative to controls varied across seizure models and reflected the different underlying neural mechanisms for each model. The ability of the technique to capture local electrical events provides a new tool in which to explore brain activity.     

Experience with the International League Against Epilepsy Classifications of Epileptic Seizures (1981) and Epilepsies and Epileptic Syndrome (1989) in Epileptic Children in a Developing Country

Four hundred eighty-three epileptic children attending the Pediatric Epilepsy Clinic at Bai Jerbai Wadia Hospital for Children, Bombay, India were classified according to the International League Against Epilepsy (ILAE) classification of epileptic seizures (1981) and epilepsies and epileptic syndromes (1989). The predominant seizures were partial (53.6), generalized (40.3%), and unclassifiable (6%). In epilepsies and epileptic syndromes, 55.3% were partial, 27% were generalized, 13.5% were undetermined, and 4.1% were special syndromes. Although our results were similar in many respects to those of other reported series, some differences were observed in the incidence of partial and generalized seizures, and partial and generalized epileptic syndromes and their subgroups, such as idiopathic, symptomatic, and cryptogenic partial syndromes, idiopathic generalized syndromes, and symptomatic specific syndromes. These differences are probably due to different age limits, methods of case ascertainment and inclusion criteria, different genetic and environmental factors, variable interpretation of clinical and EEG features, and lack of facilities for investigation in developing countries. Despite various limitations, we were able to classify most cases; the ILAE classification can be used in developing countries so that comparison can be made with other studies.     

Temporal Lobe Epilepsy in Children: Electroclinical Study of 77 Cases

Summary:  Purpose: Temporal lobe epilepsy (TLE) is probably more difficult to recognize in children than in adults. In fact, ictal symptoms in children are less stereotyped and less obvious, and the neuropathological substrate is more heterogeneous than in adults. The aim of this study is to examine the relationships between etiology, age at onset and electroclinical findings in 77 children with TLE, 32 of whom were surgically treated.
Methods: Electroclinical study including video-EEG recording of seizures in 77 children with TLE. The investigation focused on the first five initial ictal symptoms.
Results: Age at onset was less than 3 years in 39 cases, between 3 and 6 years in 17 cases and older than 6 years in 21 cases. Auras also occurred in younger children but were more common after the age of 6 years. A peculiar initial ictal semiology consisted in staring with arrest, lip cyanosis, and very slight oral automatisms. In some cases, EEG recordings documented seizures starting independently on both temporal lobes. Based on electroclinical and neuroradiological features, we recognized three subgroups: symptomatic TLE due to cortical malformations or nonevolutive tumors, TLE with mesial temporal sclerosis, and cryptogenic TLE.
Conclusions: A correct electroclinical and neuroradiological approach allows in several cases early recognition of TLE even when onset is earlier than the age of 6 years. A correct definition of the localization relies primarily on video-EEG recording of the seizures, possibly repeated during follow up in cases lacking obvious neuroradiological correlation.     

锰增强MR功能成像在猫急性戊四氮致痫模型中的初步研究

目的应用锰增强MR功能成像（ME-fMRI）检测戊四氮（PTZ）诱发的猫急性癫痫模型的脑功能激活区，探讨ME-fMRI在脑功能成像方面的应用价值。方法40只家猫，采用随机数字表法分为癫痫A、B组与对照A、B组，癫痫A、B组肌内注射PTZ55ms／ks，诱发急性癫痫发作，对照A、B组肌内注射等量生理盐水。癫痫A组与对照A组用相同的方法观察其行为改变及行脑电图检查。癫痫B组与对照B组用相同的方法行ME-fMRI检查，测量感兴趣区不同时间的信号强度，计算增强率。结果癫痫A组均成功诱发急性癫痫发作。肌内注射PTZ后，癫痫B组ME-fMRI显示大脑皮层弥漫性明显对比增强，其中额顶枕叶脑皮层增强率达（34．6±5．7）％，颞叶皮层增强率达约（22．9±6．5）％，对照组分别为（14．9±4．5）％、（11．6±3．2）％，差异有统计学意义（t值分别为-10．43、-5．46，P值均〈0．05）。海马、脑室、脑白质、基底核团、面肌增强率2组差异无统计学意义（P〉0．05）。结论肌内注射PTZ 55mg／kg能成功诱发猫急性癫痫发作；ME-fMRI能准确反映该动物模型的脑功能激活区，具有直观性、可视性、空间分辨率高等优点，在研究脑功能方面具有极大的潜能。     

氟马西尼造成的脑弥散成像改变对癫痫灶的定位研究

目的探讨癫痫患者应用氟马西尼之后,用磁共振弥散成像(diffusion-weighted magnetic imaging,DWI)检测脑组织发生的改变,从而确定癫痫灶的位置。方法选择准备手术的癫痫患者20例,其中检查前2个月内服用过苯二氮卓类药物(benzodiazepine,BZD)有9人,另取17位未发做过癫痫的健康者作为对照。在患者清醒和完全的发作间期进行磁共振弥散成像基线扫描,然后静脉推注氟马西尼(flumazenil,FMZ),注射10min后,再次进行DWI检查。所有的病人测量下列双侧结构的表观弥散系数(apparent diffusion coefficient,ADC):海马、海马旁回、丘脑、中央白质、与癫痫灶相连的皮质。健康对照者进行了DWI检查,测量了上述结构。我们还对20位患者进行了注射FMZ前后的视频脑电图比较。结果与健康对照者对比,颞叶癫痫患者发病侧海马的发作间期ADC基线明显升高(P<0.05)。在注射氟马西尼后,不同感兴趣区的平均ADC变化如下:近期服用过BZD的患者癫痫发作侧的海马ADC下降(P<0.05);癫痫发作侧的海马旁回ADC下降(P<0.05),而近期没有服用过BZD的患者,未发现上述变化。在视频脑电监测中,服用BZD的患者也更易用FMZ诱发出癫痫波。在颞叶以外癫痫我们没有观察到统一的变化模式。结论近期服用过BZD药物的颞叶癫痫患者中,注射氟马西尼引起的ADC改变和癫痫灶的位置密切相关。核磁共振弥散成像清楚地表明了颢叶癫痫患者潜在癫痫灶的位置,是一个有效检测方法。     

脑内缝隙连接

缝隙连接普遍存在于动物组织中，具有重要的生理功能。近年来，由于分子生物学等技术的应用，对许多组织的缝隙连接蛋白的特性及其功能的研究取得了很大进展。本文重点介绍脑内缝隙连接蛋白的类型，分布及其生物物理学和药理学特性，并阐述胶质细胞之间、神经元之间缝隙连接的作用，以及缝隙连接与脑发育和癫痫等神经系统疾病的关系。     

Febrile seizures - treatment and outcome

Assessment of treatment strategies in febrile seizures should be based on short- and long-term outcomes, with and without acute, intermittent, or chronic medical intervention, as well as short- and long-term side effects. Febrile seizures are a benign condition with a normal neurological, motor, intellectual, and cognitive long-term outcome and have a low risk of later epilepsy in most cases. Even many complex febrile seizures have a benign outcome. Prophylaxis may or may not reduce the recurrence rate, but does not appear to improve the long-term outcome as compared to acute treatment of seizures in progress. All agree that chronic prophylaxis with anti-epileptic agents is justified only in highly selected cases, if at all. Treatment with benzodiazepines during febrile episodes appears to effectively reduce the recurrence rate, provided adequate doses are given and compliance problems minimized. A selective approach to intermittent diazepam prophylaxis seems rational, as the recurrence risk and response to treatment are highly variable. An attractive alternative is acute treatment at seizure onset with rectal diazepam in solution given by the parents at home in order to prevent prolonged recurrent seizures. This regimen has the potential of moving the first line of anti-convulsant defence close to the child. It appears to be effective, inexpensive, feasible even for non-professionals, has few side effects and is well accepted by the parents. A reasonable policy would be to treat simple febrile seizures solely with acute rectal diazepam in solution and reserve intermittent diazepam prophylaxis for selected cases including those with multiple or prolonged recurrences, several risk factors for recurrent febrile seizures and other special situations.     

Mechanism of action of the epileptogenic drug pentylenetetrazol on a cloned neuronal potassium channel

The action of the epileptogenic agent pentylenetetrazol (PTZ) on a cloned potassium channel of the rat brain was studied. The Kv1.1 channel was expressed in oocytes ofXenopus laevis and potassium currents were investigated in outside-out and inside-out membrane patches. The results show that PTZ increased the multi-channel potassium currents at strongly negative potentials and decreased them at potentials positive to −35 mV both in outside-out and inside-out membrane patches. The extent and manner of PTZ action, the concentration dependence as well as the onset and time course of the PTZ effect were the same both in outside-out and inside-out membrane patches. The single-channel potassium currents showed an increase in open probability and frequency of opening and a decrease in close time at −50 mV and vice versa at 0 mV with application of PTZ. The amplitude of single-channel current, the open time and the latency to the first channel opening remained almost unchanged under PTZ. The results indicate that PTZ acts via the cell membrane and influences the membrane-associated part of the potassium channel. Thereby, PTZ accelerates the transition from the inactivated to the open state of the channel at strongly negative potentials and reduces it at slightly negative and positive potentials. This mechanism may be the basis for a gate function which is in favour of the development of epileptic discharges.     

Preliminary Report on Teratogenic Effects of Zonisamide in the Offspring of Treated Women with Epilepsy

Summary: Purpose: We wished to assess the risk of terato-genicity of zonisamide (ZNS) in humans.
Methods: Pregnant epileptic women treated with ZNS and their offspring were prospectively monitored from June 1989 to December 1994. The outcome of pregnancy and status of neonates were examined based on the same standardized protocol.
Results: Twenty-six offspring exposed to ZNS with or without other antiepileptic drugs (AEDs) were studied. Malformations were detected in 2 offspring (7·7%) exposed to ZNS polypharmacy. Anencephaly was detected in one case at 16 weeks of gestation (case 1, artificial abortion), and atrial septa1 defect was detected in another case at 37 weeks of gestation (case 2, delivery by cesarean section). Serum concentrations of ZNS during the first trimester of pregnancy were 6·1 μg/ml in case 1 and 6·3μ/ml in case 2; in both cases, the levels were below the therapeutic concentration range of ZNS.
Conclusions: Teratogenic effects of ZNS were not clearly defined from these results since malformations were detected in two polypharmacy cases but not in four monopharmacy cases. The present data do not indicate that the risk of ZNS teratogenicity is greater than that of other conventional AEDs. However, such risk cannot be neglected even at therapeutic dosages or concentrations of ZNS, especially in patients receiving polypharmacy.