The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–3, 2016 Ó 2016 Elsevier Inc. All rights reserved. 0736-4679/$ - see front matter http://dx.doi.org/10.1016/j.jemermed.2016.07.110 Clinical Communications: OB/GYN CATAMENIAL EPILEPSY: THE MENSTRUAL CYCLE AS A CLUE TO PREDICT FUTURE REFRACTORY SEIZURES Basem F. Khishfe, MD Department of Emergency Medicine, Mt Sinai Hospital, Chicago, Illinois Reprint Address: Basem F. Khishfe, MD, Department of Emergency Medicine, Mt Sinai Hospital, 2701 W 68th Street, Chicago, IL 60629 , Abstract—Background: Catamenial epilepsy is defined as an increase in the frequency of seizures during a particular phase of the menstrual cycle. The increased seizure frequency is attributed to the cyclic variation and neuroactive properties of endogenous steroid hormones. It is estimated that more than one-third of women with epilepsy experience catamenial seizure exacerbation. Case Report: We present the case of a young female patient who presented to the emergency department with an increase in seizure frequency that coincided with her menstrual cycle, despite complete medication compliance. Why Should an Emergency Physician Be Aware of This?: It is important for the emergency physician to consider catamenial epilepsy in the differential diagnosis for secondary causes of seizure to ensure appropriate follow-up, as well as improve the quality of life of patients suffering from uncontrolled seizures. Ó 2016 Elsevier Inc. All rights reserved. third of women with medication-refractory epilepsy experience catamenial seizure exacerbation (2). We present the case of a young female patient who presented to the emergency department with an increase in seizure frequency that coincided with her menstrual cycle, despite complete medication compliance. CASE REPORT The patient is a 26-year-old female with a medical history of seizure disorder that developed after she sustained a gunshot wound to the head at the age of 1 year. The patient presented to the emergency department after experiencing three seizures in 1 day. The patient complained of increased seizures beginning 2 to 3 days before the start of her menstrual cycle and continuing during the first 2 days of her cycle. Patient reported compliance with medications and denied any other focal symptoms. The patient had an electroencephalogram (EEG) performed at an outside hospital that documented simple partial seizures. She had been taking carbamazepine 400 mg twice daily. The patient’s physical examination was within normal limits, including a full neurologic examination. The pregnancy test was negative, basic blood work was within normal limits, and the carbamazepine level was therapeutic at 9.1 mg/mL (4.0–12.0 mg/mL). The patient underwent computed tomography of the , Keywords—catamenial; epilepsy; seizure INTRODUCTION Catamenial epilepsy is an increase in the frequency of seizures during a particular phase of the menstrual cycle. The increased seizure frequency is attributed to the cyclic variation and neuroactive properties of endogenous steroid hormones (1,2). It is estimated that more than one- RECEIVED: 14 May 2016; FINAL SUBMISSION RECEIVED: 22 July 2016; ACCEPTED: 26 July 2016 1 2 B. F. Khishfe head, given it was the first presentation to our institution, which showed no acute intracranial process. DISCUSSION Catamenial seizures affect a wide range of women of reproductive age who have epilepsy, with the wide variability attributed to the different criteria used to define seizure exacerbation (3–5). The most accepted definition of catamenial epilepsy is a twofold increase in the baseline average daily seizure activity during a particular phase of the menstrual cycle (2–3 days before and during menstruation), relative to other phases (6–9). Studies using this definition have found that approximately one-third of women with refractory epilepsy demonstrate a catamenial pattern of exacerbation (6,10,11). Catamenial patterns are more common among women with focal epilepsy, but can occur across all epilepsy types (6,9,10,12,13). One study of 100 women with intractable focal epilepsy identified catamenial patterns more often in patients with left temporal lobe foci of activity (14). In catamenial epilepsy, seizure activity tends to cluster during three phases of the menstrual cycle associated with lower ratios of progesterone to estrogen: the premenstrual period, at ovulation, or during an anovulatory or inadequate luteal phase (ILP) cycles (1,2,12). The sudden withdrawal of progesterone, resulting in an increased estradiol to progesterone ratio, is responsible for the perimenstrual pattern of seizures, where as the estradiol surge at the time of ovulation is responsible for periovulatory seizure activity. ILP and anovulatory cycles are associated with impaired progesterone production. The most common seizure pattern in catamenial epilepsy is an increase in seizure frequency immediately before or during menses. The increased seizure activity with low progesterone to estrogen ratios is attributed to the effects of estradiol and progesterone on neuronal excitability (1,6,8). Animal studies have demonstrated pro-convulsant properties of estrogen vs. progesterone that seem to have an anticonvulsant effect on neuronal activity (1). There is a positive correlation between seizure susceptibility and the estrogen to progesterone ratio, and studies indicate an association of catamenial seizures with a rapid decline in progesterone (1). Conversely, seizure frequency decreases during phases of the menstrual cycle when serum progesterone levels are high (15,16). The hepatic metabolism of anti-epileptic drugs (AEDs) is also affected by the cyclic variation of estrogen and progesterone. The premenstrual decrease in circulating estrogen and progesterone may induce hepatic en- zymes responsible for metabolism of AEDs, leading to breakthrough seizures (17). Catamenial epilepsy is a clinical diagnosis made by identifying a doubling of seizure frequency during the perimenstrual, periovulatory, or luteal phase. However, further investigation and rule out of other secondary etiologies for seizure exacerbation are still necessary. Patients should be managed with AED therapy tailored to their specific seizure type (18). A prospective study examining the efficacy of lamotrigine in women with diagnosed catamenial epilepsy demonstrated a statistically significant disappearance or 50% reduction in seizure activity during the menstrual cycle. It was noted that progesterone levels increased in women taking lamotrigine (19). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? This case report describes a patient presenting with symptoms and history consistent with catamenial epilepsy as a likely etiology for increased seizure frequency. Approximately one-third of women suffering from poorly controlled epilepsy, despite medication compliance, demonstrate a catamenial pattern of seizure exacerbation. It is therefore important for the emergency physician to consider catamenial epilepsy in the differential diagnosis for secondary causes of seizure to ensure appropriate follow-up, as well as improve the quality of life of patients suffering from uncontrolled seizures. 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