الفهرس 
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Abstract
Epilepsy is one of the most common chronic neurological disorder requiring long term or even life-long treatment with antiepileptic drugs (AEDs). These drugs adversely affect endocrine and metabolic functions, particularly relevant effects on thyroid function have been described. Subclinical hypothyroidism and alterations in thyroid hormone serum levels are reported in the literature; Phenytoin, valproate and carbamazepine, in particular, seem to be involved in these alterations. However Limited and conflicting data exists concerning the influence of antiepileptic drugs on thyroid function in children also the effects of AED use on thyroid hormones are also insufficiently investigated for newer AEDs such as oxacarbazepine, topiramate, gabapentin, lamotrigine, levetiracetam, lacosamide, zonizamide and vigabatrine.
This study aimed to investigate and to compare the effects of conventional and newer AEDs whether mono or polytherapy on thyroid profile in epileptic children and its impact on lipid profile, coagulation profile (PT, PTT and INR), weight, body mass index (BMI), rate of growth (increase of height in one year), increase in diastolic blood pressure (DBP) and trans-thoracic-echocardiogram.
Between March 2021 and June 2022, 155 Egyptian children diagnosed with epilepsy from pediatric neurology out-patient clinic at neurology department Ain Shams University Hospitals Cairo and 78 healthy participants as control group were recruited. They were sub classified to those on mono-therapy (group 1), those on poly-therapy (group 2) for more than 6 month period and age matched control group (group 3).
They were all evaluated clinically, by EEG and MRI brain. All were subjected to testing of thyroid profile, lipid profile, coagulation profile (PT, PTT and INR), weight, body mass index (BMI), and rate of growth (increase of height in one year), diastolic blood pressure (DBP) and trans-thoracic-echocardiogram.
Out of 155 patients 71(45.81 %) had partial epilepsy and 84 (54.19 %) had generalized epilepsy. Among the epileptic children there were 76 (49.03%) on mono-therapy and 79 (50.97%) on poly-therapy.Those on mono-therapy where 22 (14, 9%) patients on levitracetam, 27 (17, 42%) patients on Valproic acid, 14 (9, 03%) patients on carbamazepine and 13 (8, 39%) patients on oxacarbazepine. Those on poly-therapy were 48 (60.76%) were on two AEDs, 27 (34.18%) patients were on three AEDs and 4 patients were compliant on 4 or 5 AEDs.
Among the epileptic children in this study 85 (54.84 %) showed normal thyroid functions, 49 (31.61 %) showed hypothyroidism, 15 (9.68 %) showed subclinical hyperthyroidism and 6 (3.87 %) showed subclinical hypothyroidism. In this study 68 (43.87 %) epileptic children showed normal lipid profile and 87 (56.13 %) showed abnormal lipid profile.
There was a highly significant difference between cases and controls regarding thyroid (lower T4 and higher TSH incases), lipid profile (high total, LDL-cholesterol and lower HDL-cholesterol in cases except TG), increase height in one year (delayed growth in cases) and diastolic blood pressure (increase DBP in cases) while there was no statistically significant difference between them regarding weight and body mass index. There was also significant correlation between hypothyroid and dyslipidemia.
There was no statistically significant difference between mono-therapy and poly-therapy regarding thyroid and lipid profile, weight, BMI, rate of growth and DBP. While there was statistically significant difference between epileptic children on mono-therapy and control group and those on poly-therapy and control group regarding thyroid and lipid profile (except Triglyceride). Also there was a statistically significant difference between poly-therapy group and control group regarding decreased rate of growth and increase in DBP which is not present in monotherapy compared to control. Comparing different groups of poly-therapy (those on two AEDs, those on three AEDs and those on four or five AEDs) there was no statistically significant difference regarding thyroid, lipid profile, weight, BMI, rate of growth and DBP.
Among AEDs CBZ and PHT (enzyme inducers) as mono-therapy or poly-therapy were associated with lower T4 and higher TSH values (hypothyroidism), delayed growth and increase in diastolic blood pressure, increase in TC, LDL-C and decrease in HDL-C. VPA is associated with higher TSH level (sub-clinical hypothyroidism compared to other AEDs and it was the least affecting lipid profile compared to other AEDs but still causing dyslipidemia compared to control group. with positive dose dependant correlation between valproic acid and thyroid dysfunction. LEV was the least affecting thyroid profile compared to other AEDs but it was associated with hypothyroidism and dyslipidemia (low HDL-cholesterol level) compared to control group. OXC in high dose is similar to CBZ and act as enzyme inducer and was associated with significant Low T4 (hypothyroidism) and dyslipidemia (high TC and LDL-C). Lamotrigine is the AED not associated with alteration in thyroid profile.
Regarding the impact of thyroid state on the study parameters there was a statistically significant decreased rate of growth and increase systolic and diastolic blood pressure with hypothyroid group compared to euthyroid group also there was a statistically significant decrease rate of growth in the hypothyroid group compared to subclinical hypothyroid and subclinical hyperthyroid group, also there is a statistically significant decrease rate of growth in subclinical hyperthyroid group compared to euyhyroid group. There was also a statistically significant higher total cholesterol, LDL-cholesterol, triglyceride level and lower HDL-cholesterol in hypothyroid group compared to euthyroid group.
In conclusion; Anti –epileptic drugs mainly conventional ones are associated with hypothyroidism, sub-clinical hypothyroidism, sub-clinical hyperthyroidism, dyslipidemia and consequently delayed growth and diastolic blood. Carbamazepine (enzyme inducer) is associated with the lowest T4, higher total and LDL cholesterol level and subsequently the most delay in rate of growth and increase in DBP is observed with carbamazepine. Valproic acid associated with higher TSH with dose dependant relation and levitracetam associated with higher HDL-cholesterol level. Polytherapy significantly affects rate of growth and increase DBP. Those polytherapy containing CBZ are associated with the lowest T4, highest TSH level, lowest HDL-cholesterol level and highest DBP and those containing phenytoin are associate with most delay in rate of growth meanwhile oxacrabazepine and ethosuximide combination are associated with increased total and LDL-cholesterol.