Investigation into Mechanisms of Phenytoin Induced Cognitive Impairment in patients with Epilepsy

Abstract

The present study aimed to investigate the mechanisms involved in the cognitive impairment in newly diagnosed epileptic patients and epileptic patients under phenytoin monotherapy. Epilepsy is a common episodic neurological condition characterized by seizures with or without consciousness. Drugs used in epilepsy are categorized as first generation and second generation antiepileptic drugs (AEDs). The following were the objectives: 1. To monitor the cognitive status by using MMSE and MOCA. 2. To compare the cognitive status with homocysteine level. 3.To monitor serum phenytoin concentration in study population under phenytoin monotherapy. 4. To compare the lipid profile between newly diagnosed and epilepsy population receiving phenytoin monotherapy. 5. To assess the relationship between cognitive status, homocysteine level, lipid profile and APOE genotype among the study population. MOCA was found to be more useful tool to monitor the cognitive status. Negative correlation between cognitive status and homocysteine level (cases) proposes that homocysteine is a useful marker to assess the cognitive impairment. Cognitive impairment was found to be phenytoin dose independent. Elevated TC, TGs, HDL and VLDL was noted in study population with phenytoin monotherapy and positively correlated with homocysteine level and negatively correlated with cognitive status. APOE e4 carriers with phenytoin monotherapy were found with poor cognitive status, hyperhomocysteinemia, elevated TC, TGs, HDL and VLDL. In conclusion, the present study recommends the need of routine assessment of homocysteine level, lipid profile and APOE genotype in epilepsy patients undergoing phenytoin treatment in order to protect this population from severe cognitive impairment which may ultimately progress to Alzheimer s disease. The present study can be extended to larger epilepsy population covering different ethnic regions across the world in order to substantiate the association of APOE and#949;4 allele with cognitive impairment.