Chaves J, Sander J W
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, United Kingdom.
Epilepsia. 2005;46 Suppl 9:133-9. doi: 10.1111/j.1528-1167.2005.00325.x.
Seizures in the idiopathic generalized epilepsies (IGEs) usually remit completely with antiepileptic drugs (AEDs). Occasionally, however, they may be aggravated by AEDs. Before attributing exacerbation of seizures to an AED, alternative explanations need to be excluded. These include natural fluctuation of seizures, irregular compliance, maladjustment to the disease, comorbid illness, and development of tolerance. Aggravation may be due to a paradoxical reaction or drug-induced encephalopathy, sedative effects, or inappropriate use of a drug; and this need to be established, as it will guide management. An important caveat is that most data on aggravation of generalized seizures are based on anecdotal case reports or case series. Whether considering efficacy or aggravation, the interpretation of data from uncontrolled studies and case reports must be treated with caution. In practice, despite the fact that clear evidence is lacking, the possibility of seizure aggravation must be considered when treating people with IGEs. Predictive factors for seizure aggravation in a particular patient with a specific drug are yet to be fully defined. It is paramount to classify seizure type correctly in all patients. If this is not possible, a broad-spectrum AED should be used. Drugs that modulate Na+-channels and GABAergic drugs seem to be more prone to aggravating seizures, and therefore are best avoided in the initial management of IGE. Further studies are required to elucidate this phenomenon in full. It is interesting to speculate that paradoxical responses to AEDs may have pharmacogenetic value, serving as tools for a more precise and useful characterization of the epilepsies.
特发性全身性癫痫(IGEs)的发作通常可通过抗癫痫药物(AEDs)完全缓解。然而,偶尔它们可能会因AEDs而加重。在将癫痫发作的加重归因于一种AED之前,需要排除其他解释。这些包括癫痫发作的自然波动、依从性不规则、对疾病的适应不良、合并疾病以及耐受性的发展。加重可能是由于反常反应或药物性脑病、镇静作用或药物使用不当;这需要确定,因为它将指导治疗。一个重要的告诫是,关于全身性癫痫发作加重的大多数数据是基于轶事性病例报告或病例系列。无论是考虑疗效还是加重情况,对来自非对照研究和病例报告的数据的解释都必须谨慎对待。在实践中,尽管缺乏明确的证据,但在治疗IGEs患者时必须考虑癫痫发作加重的可能性。特定药物在特定患者中导致癫痫发作加重的预测因素尚未完全明确。对所有患者正确分类癫痫发作类型至关重要。如果无法做到这一点,应使用广谱AED。调节钠通道的药物和GABA能药物似乎更容易加重癫痫发作,因此在IGE的初始治疗中最好避免使用。需要进一步研究以充分阐明这一现象。有趣的是,可以推测对AEDs的反常反应可能具有药物遗传学价值,可作为更精确和有用地表征癫痫的工具。