Coupling Genotyping and Computational Modeling in Prediction of Anti-epileptic Drugs that cause Stevens Johnson Syndrome and Toxic Epidermal Necrolysis for Carrier of HLA-B*15:02.

PURPOSE: The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are investigated. METHODS: DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers. RESULTS: Odd ratio for CBZ induced SJS/TEN and HLA-B*15:02 was 609.0 (95% CI: 23-15873; p=0.0002). Molecular modeling studies showed that acetazolamide, ethosuxiamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone and sodium-valproate may induce ADR in HLA-B*15:02 carriers alike CBZ. Conclusion. We confirmed HLA-B*15:02 as a predictor of SJS/TEN and recommend pre-screening. Computational prediction of DIHR is useful in personalized medicine.

Factors Associated with Good Seizure Control in Patients on Valproic Acid.

OBJECTIVE: This study aims to generate a reference range for valproic acid (VPA) in this cohort and determine the factors associated with good seizure control in patients taking this drug. MATERIALS AND METHODS: We conducted a prospective, cohort, observational study among patients with epilepsy who received VPA treatment at Hospital Kuala Lumpur. The patients were considered to have good control if they had a 50% or higher seizure reduction in the one-year study period compared with the previous year. The VPA reference range was generated from those patients who had good control and whose drug concentration values were available. Multiple logistic regression analysis with a backward likelihood ratio method was applied to assess the predicting factors for good seizure control. RESULTS: A total of 242 patients were recruited and followed up for one year. The VPA reference range was determined to be 40-85 mg/L. After multivariate analysis, significant predictive variables for good control were monotherapy [adjusted OR 4.74, 95% CI: 2.258, 9.947, p<0.001], non-smoking [adjusted OR 3.23, 95% CI: 1.099, 9.473, p=0.033], normal brain imaging results [adjusted OR 5.83, 95% CI: 2.507, 13.552, p<0.001], and the absence of stress [adjusted OR 19.98, 95% CI: 9.255, 42.764, p<0.001]. CONCLUSION: Monotherapy, non-smoking, normal brain imaging results, and the absence of stress are predictive of good seizure control in patients on VPA. However, a serum concentration of VPA in the reference range failed to predict good seizure control.

Acute Disseminated Encephalomyelitis (ADEM) Presenting with Bilateral Optic Neuritis.

A 43-year old lady presented with progressive loss of vision in both eyes followed by rapid deterioration of consciousness within the next few days. This was preceded by a viral infection one week before her presentation. At presentation she had evidence of meningism and signs of bilateral upper motor neuron lesions and was managed initially as acute meningoencephalitis with antibiotics. The brain CT was within normal limits but subsequent MRI of the brain revealed multiple foci of hyperintense lesions on T2-weighted and FLAIR images. The cerebrospinal fluid examination revealed lymphocytosis, and normal protein and glucose levels. Cultures of the CSF were negative. She was managed as acute disseminated encephalomyelitis (ADEM) with high-dose of intravenous methlyprednisolone one gram/day for three consecutive days followed by oral prednisolone 60 mg/day. Despite the management she lapsed into coma and succumbed to her illness nine days after admission.