This was a single-center, prospective, observational study approved by the Ethics Committee of Zhongshan Hospital following the Declaration of Helsinki. All patients provided written informed consent and received medical examinations and interviews.
All data were collected from epilepsy patients diagnosed at the Department of Neurology, affiliated Zhongshan hospital, Xiamen University (Xiamen, China) from January 2011 to April 2016. The clinical data of the patients were collected, including age, gender, age of onset, duration of epilepsy, symptoms, etiology, epilepsy control, dose and duration of LTG, medication regimen, blood ammonia level, comorbidities, and biochemical indexes. CT or MRI was examined before medication and EEG was examined before and after medication. EEG was assessed by a specialist neuroelectrophysiologist.
The inclusion criteria were: 1. diagnosis of epilepsy according to the International Antiepileptic Alliance (ILAE);(8) 2. older than 17 years and received LTG monotherapy or combination therapy. Exclusion criteria were: 1. had hyperammonemia due to any cause except for LTG treatment such as liver failure, urea cycle defects; 2. switched to other drugs because of illness; 3. received treatment with other antiepileptic drugs (except VPA); 4. irregular medication or poor compliance; 5. pregnancy; 6. received epilepsy surgery.
Assessment of blood ammonia level
Blood samples were collected in heparinized tubes, and centrifuged at 3,000 rpm for 10 min to obtain plasma samples. The plasma ammonia was analyzed at the Department of Laboratory Medicine, Zhongshan Hospital, Xiamen University. Blood ammonia level > 60 μmol/L in male and >51 μmol/L in female were considered as hyperammonemia. According to the median of blood ammonia level (35 μmol/L), patients were divided into two groups: patients with blood ammonia level >35 μmol/L were grouped as high blood ammonia group, and the remaining patients were grouped as low blood ammonia group.
Assessment of blood LTG level
Plasma level of LTG was measured using ARK Lamotrigine assay (homogeneous enzyme immunoassay) in Siemens Viva-E automatic drug concentration analysis system.
Data analysis was performed by using SPSS version 24. Pearson chi-square and Fisher exact tests were used for classified variables. Continuous variables were compared using Mann-Whitney U test. Pearson correlation was performed to test the association between continuous variables, including plasma levels of LTG and ammonia. P-value < 0.05 was considered statistically significant.