氧惊厥大鼠脑突触体和线粒体脂质过氧化物和氨基酸递质水平的变化

观察高压氧（ＨＢＯ）惊厥大鼠脑突触体、线粒体的脂质过氧化物（ＬＰＯ）和突触体氨基酸递质水平的变化，以及抗氧化剂还原型谷胱甘肽（ＧＳＨ）预防氧惊厥的作用及其机理的探讨。方法实验用ＳＤ大白鼠，分为对照组（常压空气）、ＨＢＯ组（０．５５ＭＰａ，３０ｍｉｎ）和ＧＳＨ加ＨＢＯ组。进氧舱前３０ｍｉｎ，按８ｍｍｏｌ／ｋｇ腹腔内注射ＧＳＨ溶液或等容积０．９％ＮａＣｌ。按Ｇｒａｙ和Ｗｈｉｔｔａｋｅｒ方法制备突触体和线粒体，以Ｏｈｋｗａ方法测定ＬＰＯ含量与王自勉等方法测定突触体内氨基酸含量。结果ＨＢＯ组大鼠脑突触体和线粒体的ＬＰＯ含量显著增加，而突触体内Ｙ－氨基丁酸（ＧＡＢＡ）、牛磺酸（ｔａｕｒｉｎｅ）含量显著下降；氧暴露前预先给予ＧＳＨ，可防止ＨＢＯ引起的突触体内ＧＡＢＡ水平的降低，减少突触体ＬＰＯ的生成。结论氧惊厥的发生与脑内氧自由基生成增加，引起突触体和线粒体膜脂质过氧化作用增强，以及神经递质代谢紊乱有关。     

胃肠炎伴无热惊厥42例婴幼儿临床研究

目的研究胃肠炎伴婴幼儿无热惊厥患儿惊厥的性质。方法对42例因胃肠炎伴无热惊厥的婴幼儿进行临床资料分析和随访。结果42例中出院诊断为轻度胃肠炎伴良性婴幼儿惊厥（BICE）32例,门诊随访1—3年后有3例因反复发作、脑电图异常诊断为癫痫;2例各复发1次,但脑电图正常,考虑为BICE复发,门诊随访中。42例中5例因脑电图检查可见痫样放电,而诊断为癫痫发作,2例诊断为病毒性脑膜脑炎,3例诊断为电解质、血糖紊乱引起。结论胃肠炎伴无热惊厥的婴幼儿病因复杂,如无阳性检查结果,既往无惊厥病史的病人大部分（29／42）是BICE患儿,但需神经门诊长期随访,部分病人随诊后诊断为癫痫,少部分病人可出现复发,且惊厥发作的出现有早于胃肠炎的病例。     

Post-Traumatic Epilepsy: Cellular Mechanisms and Implications for Treatment

Summary: Epilepsy complicates severe head trauma. Development of persistent seizures appears to correlate with the extent of trauma. Although early reports suggested that prophylactic administration of antiepileptic drugs would prevent epileptogenesis, controlled studies have failed to corroborate this assumption. Head trauma initiates a sequence of responses that includes altered blood flow and vasoregulation, disruption of the blood-brain barrier, increases in intracranial pressure, focal or diffuse ischemia, hemorrhage, inflammation, necrosis, and disruption of fiber tracts. The presence of an intracranial hematoma has a robust association with the development of post-traumatic epilepsy. Extravasation of blood is followed by hemolysis and deposition of heme-containing compounds into the neuropil, initiating a sequence of univalent redox reactions and generating various free radical species, including superoxides, hydroxyl radicals, peroxides, and perferryl ions. Free radicals initiate peroxidation reactions by hydrogen abstraction from methylene groups adjacent to double bonds of fatty acids and lipids within cellular membranes. Intrinsic enzymatic mechanisms for control of free radical reactions include activation of catalase, peroxidase, and superoxide dismutase. Steroids, proteins, and tocopherol also terminate per-oxidative reactions. Tocopherol and selenium are effective in preventing tissue injury initiated by ferrous chloride and heme compounds. Treatment strategies for prevention or prophylaxis of post-traumatic epilepsy must await absolute knowledge of mechanisms. Antioxidants and chelators may be useful, given the speculation that peroxidative reactions may be an important component of brain injury responses. However, potential treatment strategies involving -y-aminobutyric acid (GABA) agonists, NMDA receptor antagonists, and barbiturates need further scientific assessment.     

新生儿惊厥176例临床分析

目的讨探新生儿惊厥的病因、临床表现特点,以有效控制惊厥的发作,早期干预减少后遗症。方法对我院新生儿科的176例新生儿惊厥患儿的临床资料进行回顾性分析。结果显示以缺氧缺血性脑病和颅内出血多见,发病时间多在生后3 d内;其次为低血钙和低血糖,发病时间多在生后1周;而感染多发生于1周后。结论早期发生惊厥者主要与围产期窒息有关,本组缺氧缺血性脑病占首位,其次是颅内出血,常在出生12~24 h发病,出生1周后发病者应考虑感染和电解质紊乱。因此强调加强围产期保健,提高产科技术,建立高危新生儿监护的重要性,早期干预,有助于降低发病率、病死率及后遗症。     

A mitochondrial encephalomyopathy: the first case with an established defect at the level of coenzyme Q

A patient is presented who had therapy-resistant epileptic seizures from the 7th day of life. Examination at the age of 17 months revealed a mentally retarded boy with epileptic seizures, generalised myoclonic contractions, and abnormal ocular movements. A cerebral CT scan showed central and cortical atrophy. Lactate levels in serum, cerebrospinal fluid and urine were elevated, the pyruvate level was raised in serum. A quadriceps muscle biopsy revealed aspecific morphologic signs of a myopathy. Biochemical analysis showed decreased substrate oxidation rates in the mitochondria associated with low rates of ATP production. Total and free carnitine levels were decreased. Investigation of the respiratory chain revealed a defect in the proximal part of respiratory chain revealed a defect in the proximal part of respiratory chain involving the region of coenzyme Q. Based on clinical and chemical data it is likely that the patient is suffering from a multi-system disorder.Abbreviations EEG electroencephalogram - CT computed tomography - CSF cerebrospinal fluid - Ap₅A P, P⁵-di(adenosine-5-)pantaphosphate - BSA bovine serum albumin - CPT carnitine palmitoyltransferase - SCC succinate: cytochrome c oxidoreductase - SQ succinate:coenzyme Q oxidoreductase - DCPIP 2,6-dichlorophenol indophenol This investigation is part of the research program Disorders of the Neuromuscular System     

Unprovoked seizures after complex febrile convulsions

Children with complex febrile convulsions bear a higher risk of developing epilepsy than children with simple febrile convulsions. Complex febrile convulsions are defined by the presence of prolonged seizures, partial seizures and multiple seizures occurring during the same day. The aim of this study is to delineate the relative significance of each of the three criteria defining complex febrile convulsions. Fifty-seven out of 477 children (12%) admitted for febrile convulsions had complex febrile convulsions and normal neurological examination. Follow-up was available for 48 (84%) of them. Thirteen of these 48 (27%) had epilepsy at follow-up. The mean age of seizure onset among the patients with subsequent afebrile seizures was significantly lower than the rest (10.8 months versus 16.8 months). The patients with partial febrile convulsions showed a trend toward a higher risk (45%) of developing epilepsy than the patients with multiple febrile convulsions (21%).     

Efficacy of biperiden and atropine as anticonvulsant treatment for organophosphorus nerve agent intoxication

The ability of the nerve agents tabun, sarin, soman, GF, VR, and VX to produce brain seizures and the effectiveness of the anticholinergics biperiden HCl or atropine SO₄ as an anticonvulsant treatment were studied in a guinea-pig model. All animals were implanted a week prior to the experiment with cortical electrodes for electroencephalogram (EEG) recordings. On the day of exposure, the animals were pretreated with pyridostigmine (0.026 mg/kg, i.m.) 30 min prior to challenge with a 2 × LD₅₀ dose (s.c.) of a given agent. In separate experiments, animals were challenged with 5 × LD₅₀ (sc) of soman. One minute after agent challenge, the animals were treated intramuscularly (i.m.) with 2 mg/kg atropine SO₄ admixed with 25 mg/kg 2-PAM Cl and then observed for the onset of seizure activity. Five minutes after the start of nerve agent-induced EEG seizures, animals were treated i.m. with different doses of biperiden HCl or atropine SO₄ and observed for seizure termination. The anticonvulsant ED₅₀ of biperiden HCl and atropine SO₄ for termination of seizures induced by each nerve agent was calculated and compared. With equally toxic doses (2 × LD₅₀) of these agents, continuous EEG seizures (status epilepticus) developed in all animals challenged with soman, tabun, or VR, and in more than 90% of the animals challenged with GF or sarin. In contrast, only 50% of the animals developed seizures when challenged with VX. The times to onset of seizures for soman, tabun, GF, and sarin were very similar (5–8 min) while for VR, it was about 10 min. In the case of VX, not only was the time to seizure development longer (20.7 min), but the seizure activity in 19% of the animals terminated spontaneously within 5 min after onset and did not return. Under these conditions, the anticonvulsant ED₅₀s of biperiden HCl for soman, GF, VR, tabun, sarin, and VX were 0.57, 0.51, 0.41, 0.2, 0.1, and 0.09 mg/kg, respectively, while those of atropine SO₄ for soman, VR, tabun, GF, sarin, and VX were 12.2, 11.9, 10.4, 10.3, 5.1, and 4.1 mg/kg, respectively. In separate experiments, the anticonvulsant ED₅₀ doses of biperiden for animals challenged with 2 or 5 × LD₅₀ of soman were 0.48 (95% confidence limits 0.25–0.73) or 0.57 (95% CI 0.38–0.84) mg/kg, respectively, while the anticonvulsant ED₅₀s for atropine (12.2 mg/kg, i.m.) were identical under these same two challenge conditions. The present study demonstrates that all nerve agents can produce status epilepticus and that the therapeutic effectiveness of atropine and biperiden roughly paralleled the seizurogenic potential of these agents. Received: 16 November 1999 / Accepted: 9 February 2000     

Convulsions elicited by handling: A sensitive method of measuring CNS excitation in mice treated with reserpine or convulsant drugs

Mice treated with reserpine, picrotoxin or pentylenetetrazol showed convulsions on handling. These seizures closely resembled the previously described convulsions on handling in mice undergoing alcohol withdrawal reactions. The mildest form of the convulsion was tonic, in a characteristic posture, and was evoked by gently spinning the mouse by the tail. More severely affected mice showed clonic seizures when simply lifted by the tail. Reserpine-treated mice had no spontaneous seizures but convulsions could be repeatedly elicited by handling for about 24 h after a single dose. Mice treated with picrotoxin or pentylenetetrazole showed elicited convulsions at doses that were too low to cause spontaneous seizures or at times when the overt convulsant action had ceased. The number of mice showing elicited convulsions was dose-related. Strychnine treatment caused convulsions on handling only at near-lethal doses and then in only a few mice. Convulsions on handling may be useful as a simple empirical sign of CNS hyperactivity in mice.This work was supported by a grant from the U. S. Brewers Association.     

Tolerance to cocaine-induced convulsions in the cat

Two groups of female cats (6 each) were used: (1) a seizure group which received a minimum convulsive dose (MCD) of cocaine i.v., and (2) a subseizure group which received a subconvulsive dose of cocaine i.v., for 13 successive days. Determination of the MCD across 13 days in the seizure group and on Day 14 in the subseizure group revealed significant tolerance to cocaine-induced convulsions. However, reverse tolerance to cocaine-induced abnormal behavior developed as dystonic posture and speed of stereotyped movement increased during the 13-day treatment period in the subseizure group. These data are discussed in terms of local anesthetic and catecholaminergic effects of cocaine, as well as possible differential effects of various routes of administration.     

Differential blockade of bicuculline convulsions by neuroleptics.

Haloperidol, pimozide, sulpiride and metoclopramide blocked bicuculline-induced convulsions in mice. Chlorpromazine and thioridazine exhibited this effect at low doses whereas at higher doses (e.g. 1 mg/kg i.p. chlorpromazine) this activity was no longer apparent. A dose of phenoxybenzamine which was inactive alone (7.5 mg/kg i.p.) completely blocked the anti-bicuculline effect of sulpiride and antagonized that of haloperidol. These data are interpreted as indicating that intact noradrenergic systems are necessary for the anti-bicuculline effect of the neuroleptics.