阵发性运动障碍25例临床分析

目的总结阵发性运动障碍患者的诱发因素、临床特征以及治疗特点。方法收集阵发性运动障碍患者25例,均进行神经科常规检查以及视频脑电和核磁共振扫描,部分患者进行单光子发射计算机断层扫描,并对其诱发因素、发病年龄以及临床表现进行分析,观察对抗癫药物治疗的效果。结果25例患者中,散发14例,有家族史患者8例,继发性3例。其中阵发性运动源性舞蹈样徐动症/运动障碍共19例,对小剂量卡马西平治疗有显著效果。结论不同类型的阵发性运动障碍诱发因素不同,对卡马西平的治疗效果也不同;继发性阵发性运动障碍要重视原发病治疗。     

Changes of seizures activity during rapid withdrawal of lamotrigine

Quantitatively evaluating the rapid withdrawal effects of lamotrigine (LTG) and carbamazepine (CBZ) on seizure activity during pre-surgical evaluation in patients with pharmacoresistant complex partial epilepsy. The duration and frequency of seizure activities and electrographic seizure onset of 41 patients totally withdrawing from CBZ monotherapy (n = 20), LTG monotherapy (n = 10) and CBZ + LTG combined therapy (n = 11) were intensively studied by therapeutic intensive seizure analysis (TISA) method. Study phases ran from the baseline phase to the antiepileptic drug (AED) withdrawal phase until the AED free phase, 3 days for each phase. Seizure duration and frequency obviously increased during the withdrawal process in each group (P < 0.05). The duration of secondarily generalized clonic signs markedly increased with the tapering of each drug; tonic signs, however, only in the AED free phase (P < 0.05). The frequency of secondary tonic and clonic signs only increased in the CBZ and CBZ + LTG group. Intergroup comparisons of all variables were insignificant (P > 0.05). There was no change of ictal EEG localization during all withdrawal protocols. All patients experienced more severe seizures during the withdrawal processes. An earlier aggravation of the clonic signs than the tonic signs was observed in each group. Difference between the withdrawal effects of LTG and CBZ monotherapy and LTG + CBZ polytherapy was mainly in the frequency change of ictal signs. The withdrawal process did not influence the ictal EEG localization. This study justified the withdrawal in pre-surgical localization, rationalized precautions for possible accompanying risks, and also aroused attentions in clinical anticonvulsant trials and substitutions involving withdrawal process.     

Response of Obsessive Compulsive Disorder to Carbamazepine in Two Patients with Comorbid Epilepsy

An association between epilepsy and obsessive compulsive disorder (OCD) has been noted. The response of two patients with OCD and comorbid epilepsy to carbamazepine is reported. It is hypothesized that obsessive compulsive symptoms may be a variant of epileptiform forced thinking in a subgroup of patients, and may be preferentially responsive to anticonvulsant therapy.     

A history of investigation on the mood stabilizing effect of carbamazepine in Japan

Abstract A history of investigation on the antimanic and prophylactic effects of carbamazepine in Japan is described. Following the initial open trials in the early 1970s in which the antimanic and prophylactic effects of carbamazepine were indicated for the first time in the world, the mood stabilizing effect was confirmed by the double blind studies which were performed with a multi-institutional cooperation in Japan in the late 1970s. During the course of the double blind trials, the problem of different therapeutic dosages of psychotropic drugs between Japan and Western countries emerged; that is, the doses of chlorpromazine and lithium carbonate, which were used as the control drugs to carbamazepine in the two double-blind group-comparison studies in Japan, were both much lower than the dosage used in most of the Western countries. The low dosage of control drugs made the evaluation of the results of the double blind studies performed in Japan difficult, and caused a delay of publication in the Western journals of the results. Whether the difference is due to biological factors or to psychosocial and cultural factors is an important problem in psychopharmacology and should be investigated further.     

用高效液相色谱法测定血清卡马西平及其代谢产物浓度

本文报告了一个可同时测定卡马西平及其少在40mg·L~(-1)内呈线性,1O,11一环氧卡马西平活性代谢产物血药浓度的高效液相色谱法。于至少在20mg·L~(-1)内呈线性。0.3ml血清样本中加入内标物(10—甲氧卡马西平)后.经4mol·L~(-1)氢氧化钠碱化.用二氯甲烷提取;提取液在室温中氮气流下挥干、流动相重组进样.进行色谱分析。以乙腈/甲醇/水(50/210/260.V/V)为流动相.以C_(18)反相桂(150×4.6mm)为固定相,检测波长为214nm。本法卡马西平及1O,11—环氧卡马西平的最小检出浓度分别为0.08mg·L~(-1)和0.1mg·L~(-1).平均绝对回收率分别为96.0％和97.3％;日内变异系数为3.3％～5.7%.日间变异系数为4.3％～9.0％;卡马西平至     

Carbamazepine and bone mineral metabolism

The status of bone mineral metabolism was studied in 21 epileptic out-patients receiving carbamazepine as the sole anticonvulsant drug. Hypocalcaemia was found in 3, hypophosphataemia in one and elevated serum alkaline phosphatase in 4 of the cases. Serum 25-hydroxyvitamin D values were significantly lower in the patients than in the controls. No statistically significant difference was observed in bone mineral density between the patients and controls. Histomorphometric analysis of the iliac crest cancellous bone did not reveal any statistically significant difference in the amount of trabecular bone or osteoid between the patients and controls, but the patients had an increased amount of trabecular resorption surfaces. An increased amount of osteoid, suggesting histological osteomalacia, was found in 2 of the 18 biopsies. We conclude that epileptic out-patients receiving carbamazepine therapy have vitamin D deficiency and may develop osteomalacic changes in their skeleton.     

Possible role of adenosine receptors in psychiatric diseases

Effective antidepressive treatments like electroconvulsive therapy and sleep deprivation increase adenosine A₁-receptors in the brains of experimental animals. It has therefore been of considerable interest that carbamazepine, which is known to be clinically similarly effective as lithium ions in the prophylaxis of affective illness, interacts with adenosine receptors. We have recently characterized this interaction using cellular model systems, in which adenosine receptor subtypes evoke different second messenger responses. The results show that carbamazepine at therapeutically relevant concentrations, is a selective antagonist of the A₁- but not of the high affinity A₂-receptor subtype. The increase in the frequency and severity of the episodes that is often observed in the course of affective illness has been interpreted as the result of plastic changes in neuronal sensitivity that lead to the development of pathologically supersensitive neural circuits. The prophylactic properties of lithium ions are thought to be due to a dampening of the inositol-phospholipid second not directly influence the generation of inositol phosphates. However, adenosine-agonists, presumably acting via A₁-receptors, can potently modulate the neurotransmitter-evoked increase of inositol phosphates and cytosolic free calcium ions. This effect could play a role in synaptic plasticity. Indeed, A₁-agonists can block the development of “long term potentiation,” a model of synaptic plasticity. We suggest that the prophylactic properties of carbamazepine in affective psychoses might be related to the inhibition by carbamazepine and the subsequent supersensitization of the A₁-receptors that modulate the neurotransmitter-induced formation of inositol phosphates and synaptic plasticity. © 1993 Wiley-Liss, Inc.     

Reduced carnitine and antiepileptic drugs: cause relationship or co-existence?

Serum carnitine was measured longitudinally before and after therapy in 15 patients receiving valproic acid, 14 patients receiving carbamazepine and 8 patients receiving phenobarbital. The patients who received valproic acid showed a significant reduction in free (and total) serum carnitine (mean (SE) 37.6 (6.2)/umol/l without valproic acid, 29.1 (1.6)/xmol/l with valproic acid (p < 0.001)). Such an effect was not found in patients receiving carbamazepine or phenobarbital.     

不同剂量卡马西平在家兔体内的药物动力学

本文采用高效液相法（ＨＰＬＣ）测定了卡马西平的血药浓度，在１８只家兔体内观察不同剂量下药物浓度变化和药动学参数差异。结果发现家兔在两种剂量下均有双峰现象，这一现象估计与肠－肝循环有关，两组剂量的Ｔ１／２间有显著差异，高剂量组的平均Ｔ１／２比低剂量的下降一半。这一结论应引起临床医师的注意     

Plasma levels of carbamazepine and carbamazepine-10,11-epoxide during treatment of epilepsy

Summary Carbamazepine and its epoxide in plasma were measured by liquid chromatography in 25 patients treated with a mean dose of carbamazepine of 12.5±3.3 mg/kg body weight. The mean concentrations of parent drug and metabolite were 5.4±2.5 µg/ml and 1.10±0.42 µg/ml, respectively. A significant correlation was found between the plasma concentrations of the two compounds (r=0.64; p<0.001), but marked interindividual variation existed in the ratio of carbamazepine to epoxide. Based on simultaneous measurements in plasma and cerebrospinal fluid, the unbound fraction of carbamazepine in plasma was of the order of 20% as compared to 45% for the epoxide. Thirteen ambulant patients suffering from partial epilepsy with complex symptomatology, who were already being treated with phenytoin in optimal doses (plasma level 14–20 µg/ml) were also given carbamazepine. At plasma levels of the latter of about 5 µg/ml there was no further reduction in the frequency of partial or generalized epileptic seizures. In five patients the dose was increased to produce plasma concentrations of 7 – 8 µg/ml. There was still no improvement and side-effects were seen in three patients.