Treiman D M
Neurology Service, Veterans Administration West Los Angeles Medical Center 90024.
Epilepsia. 1989;30 Suppl 3:S31-5. doi: 10.1111/j.1528-1157.1989.tb05831.x.
The goal of management in epilepsy is to make patients completely seizure-free without side effects. Currently, this goal can be achieved fully in only about one-half of the 50,000,000 people in the world with epilepsy. Epilepsy is not a benign condition. Uncontrolled epilepsy produces significant morbidity and mortality. Even infrequent seizures put a patient at risk of sudden death and compromise employability and other social functions. The potential risk of a new antiepileptic drug has to be weighted against the potential risk of continuing seizures and the potential for the new drug to control those seizures. Vigabatrin (gamma vinyl GABA, GVG) is one of the promising new antiepileptic drugs now under development. In four large clinical trials half of the patients in each trial had a greater than or equal to 50% reduction in seizure frequency when GVG was added to existing antiepileptic drug. This represents a significant response rate in add-on trials, which are a severe test of a new antiepileptic drug. Although microvacuoles have been seen in the white matter of the brains of rats and dogs treated with GVG, such pathological changes have not yet been observed in humans. Evoked potential studies have failed to reveal any evidence of microvacuolization in humans. Because of the potential efficacy of GVG in controlling previously therapeutic-resistant seizures and of the absence of evidence of significant toxicity in humans, carefully monitored clinical trials of GVG in therapy-resistant patients with epilepsy should continue.
癫痫治疗的目标是使患者完全无癫痫发作且无副作用。目前,全球约5000万癫痫患者中,只有大约一半的人能完全实现这一目标。癫痫并非良性疾病。癫痫不受控制会导致严重的发病率和死亡率。即使是偶尔发作也会使患者面临猝死风险,并影响就业能力和其他社会功能。一种新型抗癫痫药物的潜在风险必须与持续癫痫发作的潜在风险以及该新药控制这些发作的可能性进行权衡。氨己烯酸(γ-乙烯基氨基丁酸,GVG)是目前正在研发的有前景的新型抗癫痫药物之一。在四项大型临床试验中,当在现有抗癫痫药物基础上加用GVG时,每项试验中有一半患者的癫痫发作频率降低了50%或更多。这在添加治疗试验中代表了显著的有效率,而添加治疗试验是对新型抗癫痫药物的严格考验。尽管在用GVG治疗的大鼠和犬的脑白质中发现了微空泡,但在人类中尚未观察到这种病理变化。诱发电位研究也未发现人类有微空泡形成的任何证据。鉴于GVG在控制先前治疗耐药性癫痫发作方面的潜在疗效,以及在人类中缺乏明显毒性的证据,应继续在耐药性癫痫患者中对GVG进行仔细监测的临床试验。