Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For diagnosis of seizure type and epilepsy syndrome, we always take all the three aspects of 1) history and symptoms (symptomatology), 2) EEG (clinical neurophysiology) and 3) neuroimaging into account, and thus an appropriate treatment approach based on both short- and long-term concerns is individualized. Recent advances in clinical epileptology on the three aspects (i, ii, iii) and on genetic analysis (iv, v) are briefly introduced as follows. i) Wide-band EEG analysis Clinical EEG provides us with diagnostic information of epileptogenicity by epileptiform discharges, i.e., spikes, sharp waves, which reflects the paroxysmal depolarization shifts (PDS) in the epileptic neurons. Currently advanced technology has enabled us to record wide-band EEG: direct current (DC) shifts (Ikeda et al., 1996) and high frequency oscillation (HFO) (Bragin et al., 1999). The both conditions occurred together as early as electrodecremental pattern occurred or earlier than conventional ECoG changes, and that ictal DC shifts happened earlier than HFO on some occasions, that may suggest more active role of glia (Imamura et al., 2011). ii) Amygdalar enlargement in patients with temporal lobe epilepsy (TLE). With absence of hippocampal atrophy (HA), some patients with TLE clearly showed amygdalar enlargement on focus side; they had older onset age and better seizure control than HA. It may be a subtype of TLE (Mitsueda-Ono et al., 2011). iii) Focal epilepsy syndrome as antibody-mediated gray matter disease? Recently delineated antibodies to cell surface antigens such as anti-VGKC antibody, anti-GAD antibody or anti-NMDA receptor antibody could develop chronic epileptic condition, being apart from so-called acute limbic encephalitis with ovarian teratoma. iv) Gentic abnormality in epilepsy other than channelopathy Abnormality of LGI1 gene is responsible for autosomal dominant lateral temporal lobe epilepsy (ADLTE), where synaptic transmission could be impaired. Clinically significant divergence in symptoms and the degree of abnormality within family as well as between families remains to be solved (Kawamata et al., 2010). v) Genetic polymorphism in CYP2C19 in drug choice Information of genetic polymorphism in CYP2C19 could individualize drug choice and its dose in advance (Yasuda et al., 2009).
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PMID:[The leading edge of epilepsy research]. 2227 54

Phenytoin (PHT) is an antiepileptic drug widely used in the treatment of focal epilepsy and status epilepticus, and effective in controlling focal seizures with and without tonic-clonic generalization and status epilepticus. The metabolization of PHT is carried out by two oxidative cytochrome P450 enzymes CYP2C9 and CYP2C19; 90% of this metabolization is done by CYP2C9 and the remaining 10% by CYP2C19. Genetic polymorphism of CYP2C9 may reduce the metabolism of PHT by 25-50% in patients with variants *2 and *3 compared to those with wild-type variant *1. The frequency distribution of CYP2C9 polymorphism alleles in patients with epilepsy around the world ranges from 4.5 to 13.6%, being less frequent in African-Americans and Asians. PHT has a narrow therapeutic range and a nonlinear pharmacokinetic profile; hence, its poor metabolization has significant clinical implications as it causes more frequent and more serious adverse effects requiring discontinuation of treatment, even if it had been effective. There is evidence that polymorphisms of CYP2C9 and the use of PHT are associated with an increase in the frequency of some side effects, such as cerebellar atrophy, gingival hypertrophy or acute cutaneous reactions. The presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis; hence, PHT should not be prescribed in these patients. In patients with CYP2C9 *1/*2 or *1/*3 alleles (intermediate metabolizers), the usual PHT maintenance dose (5-10 mg/kg/day) must be reduced by 25%, and in those with CYP2C9 *2/*2, *2/*3 or *3/*3 alleles (poor metabolizers), the dose must be reduced by 50%. It is controversial whether CYP2C9 genotyping should be done before starting PHT treatment. In this paper, we aim to review the influence of CYP2C9 polymorphism on the metabolization of PHT and the clinical implications of poor metabolization in the treatment of epilepsies.
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PMID:CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment. 2963 28