A 29-year-old woman comes to the clinic for routine follow-up. Five years ago, she experienced an unprovoked generalized tonic-clonic seizure. At that time, phenytoin was prescribed, and the patient has been on a stable dose since. She has not experienced seizure recurrence. MRI of the brain performed following the initial episode was normal. She has no other medical problems and is a lifetime nonsmoker. The patient's family history is negative for neurologic disease. She is in a stable relationship and is contemplating pregnancy. Blood pressure is 123/72 mm Hg and pulse is 75/min. Neurologic examination is unremarkable. Serum phenytoin level is 11 mcg/mL (therapeutic range, 10-20 mcg/mL). Electroencephalogram is normal. Which of the following is the best next step in management of this patient?

Question

A 29-year-old woman comes to the clinic for routine follow-up.  Five years ago, she experienced an unprovoked generalized tonic-clonic seizure.  At that time, phenytoin was prescribed, and the patient has been on a stable dose since.  She has not experienced seizure recurrence.  MRI of the brain performed following the initial episode was normal.  She has no other medical problems and is a lifetime nonsmoker.  The patient's family history is negative for neurologic disease.  She is in a stable relationship and is contemplating pregnancy.  Blood pressure is 123/72 mm Hg and pulse is 75/min.  Neurologic examination is unremarkable.  Serum phenytoin level is 11 mcg/mL (therapeutic range, 10-20 mcg/mL).  Electroencephalogram is normal.  Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

Discontinuing phenytoin in this patient who has a history of unprovoked seizure but has been seizure free >2 years is a reasonable consideration. Given her lack of identifiable brain disease, normal EEG, absence of familial epilepsy, and positive initial response to therapy, this patient is at a low risk for seizure recurrence. In addition, phenytoin is a known teratogen capable of causing fetal hydantoin syndrome (eg, orofacial clefts, microcephaly, nail/digit hypoplasia, cardiac defects, dysmorphic facial features). Given its known teratogenicity, phenytoin should be discontinued in women of reproductive age who are considering becoming pregnant and have a low risk of seizure recurrence. A personalized slow taper is indicated as rapid withdrawal may result in seizure recurrence (Choice A). (Choice B) Increasing the dose of phenytoin in this patient who has a 5-year seizure-free period and is considering becoming pregnant is inappropriate; it would expose her to additional dose-dependent side effects (eg, drowsiness, diplopia, ataxia) and increase the likelihood of her offspring being born with congenital defects. (Choice C) Brain MRI is indicated as part of the initial workup of new-onset seizure in adults to identify structural abnormalities (eg, tumor, infarction). However, follow-up MRI is unlikely to provide additional useful information in this patient, who has a previously normal MRI, has remained seizure free, and has a normal neurologic examination. (Choice E) Like phenytoin, valproic acid is an antiepileptic drug that has been linked to an increased risk of congenital anomalies such as neural tube defects (eg, spina bifida) and dysmorphic facial features. Educational objective: Phenytoin is an antiepileptic drug with known teratogenic effects (eg, fetal hydantoin syndrome). Women of childbearing age who have a low risk of seizure recurrence may safely discontinue phenytoin if considering becoming pregnant; however, the medication should be slowly tapered as rapid withdrawal may result in seizure recurrence. References: Stopping antiepileptic drugs: when and why? (http://www.ncbi.nlm.nih.gov/pubmed/20730110) Pregnancy, epilepsy, and anticonvulsants. (http://www.ncbi.nlm.nih.gov/pubmed/18472485)

A 29-Year-Old Woman Comes to the Clinic for Routine Follow-Up