Takeoka Masanori, Riviello James J, Pfeifer Heidi, Thiele Elizabeth A
Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Children's Hospital, Boston, Massachusetts, USA.
Epilepsia. 2002 Sep;43(9):1072-5. doi: 10.1046/j.1528-1157.2002.00602.x.
Topiramate (TPM) is widely used as add-on therapy for epilepsy. TPM inhibits carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate. The ketogenic diet (KGD) predisposes patients to metabolic acidosis, especially during induction. In children with refractory epilepsy, cotreatment with TPM and KGD may be considered, but special attention should be paid to the combined risks for metabolic acidosis and nephrolithiasis. We report our experience in 14 children cotreated with TPM and the KGD.
Medical records of 14 children cotreated with the KGD and TPM for medically refractory epilepsy were reviewed retrospectively. Bicarbonate levels were analyzed and correlated with clinical profiles, including duration of cotreatment, TPM dose, KGD ratio, and seizure control.
Nine children had a <20% decrease in bicarbonate levels, from 5.3 to 12.3 mEq/L (mean, 7.6 mEq/L). Cotreatment was continued in all patients for duration of 33 to 544 days (seven had remained on cotreatment at the end of the study period), although two children required bicarbonate supplements to continue the KGD. No patient had nephrolithiasis.
Although a large decrease in bicarbonate level occurred in the majority of children, the decrease appeared mostly at the time of KGD induction when added to prior TPM therapy. Bicarbonate levels should be monitored carefully with TPM and KGD cotreatment, and bicarbonate supplements given when symptomatic.
托吡酯（TPM）被广泛用作癫痫的附加治疗药物。TPM可抑制碳酸酐酶，这可能导致血清碳酸氢盐减少而引起代谢性酸中毒。生酮饮食（KGD）使患者易发生代谢性酸中毒，尤其是在诱导期。对于难治性癫痫患儿，可考虑TPM与KGD联合治疗，但应特别关注代谢性酸中毒和肾结石的合并风险。我们报告了14例接受TPM与KGD联合治疗患儿的经验。
回顾性分析14例接受KGD与TPM联合治疗难治性癫痫患儿的病历。分析碳酸氢盐水平，并与临床特征进行相关性分析，包括联合治疗持续时间、TPM剂量、KGD比例和癫痫控制情况。
9例患儿的碳酸氢盐水平下降<20%，从5.3降至12.3 mEq/L（平均7.6 mEq/L）。所有患者的联合治疗持续33至544天（7例在研究期末仍在接受联合治疗），尽管有2例患儿需要补充碳酸氢盐以继续进行KGD治疗。无患儿发生肾结石。
虽然大多数患儿的碳酸氢盐水平大幅下降，但这种下降大多出现在KGD诱导期加用先前的TPM治疗时。TPM与KGD联合治疗时应仔细监测碳酸氢盐水平，出现症状时给予碳酸氢盐补充剂。
