CATAMENIAL EPILEPSY THE MENSTRUAL CYCLE AS A CLUE TO PREDICT FUTURE REFRACTORY SEIZURES

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. Patients
with suspected catamenial epilepsy should be counseled
to avoid driving or climbing ladders near the time of their
menstrual cycle.
REFERENCES
1. Verrotti A, D’Egidio C, Agostinelli S, et al. Diagnosis and management of catamenial seizures: a review. Int J Womens Health 2012;4:
535–41.
2. Kim GH, Lee HW, Park H, et al. Seizure exacerbation and hormonal
cycles in women with epilepsy. Epilepsy Res 2010;90:214–20.
3. Duncan S, Read CL, Brodie MJ. How common is catamenial epilepsy? Epilepsia 1993;34:827–31.
4. Kariyawasam SH, Mannapperuma U, Jayasuriya WJ, et al. Occurrence of menstrual cycle related seizure patterns among epileptic
women attending the tertiary neurology clinics of the National Hospital of Sri Lanka. Epilepsy Res 2009;84:257–62.
5. Bazán AC, Montenegro MA, Cendes F, et al. Menstrual cycle worsening of epileptic seizures in women with symptomatic focal epilepsy. Arq Neuropsiquiatr 2005;63:751–6.
6. Herzog A, Klein P, Ransil B. Three patterns of catamenial epilepsy.
Epilepsia 1997;38:1082–8.
7. Herzog A. Catamenial epilepsy: definition, prevalence pathophysiology and treatment. Seizure 2008;17:151–9.
8. Foldvary-Schaefer N, Falcone T. Catamenial epilepsy: pathophysiology, diagnosis, and management. Neurology 2003;61(suppl 2):
S2–15.
Catamenial Epilepsy
9. Reddy D. The role of neurosteroids in the pathophysiology and
treatment of catamenial epilepsy. Epilepsy Res 2009;85:1–30.
10. El-Khayat H, Soliman N, Tomoum H, et al. Reproductive hormonal
changes and catamenial pattern in adolescent females with epilepsy.
Epilepsia 2008;49:1619–26.
11. Herzog A, Harden C, Liporace J, et al. Frequency of catamenial
seizure exacerbation in women with localization-related epilepsy.
Ann Neurol 2004;56:431–4.
12. Herzog A, Fowler K, Sperling M, et al. Progesterone Trial Study
Group. Variation of seizure frequency with ovulatory status of menstrual cycles. Epilepsia 2011;52:1843–8.
13. Morrell M, Hamdy S, Seale C, et al. Self-reported reproductive history in women with epilepsy: puberty onset and effects of menarche
and menstrual cycle on seizures. Neurology 1998;50:448.
3
14. Quigg M, Smithson S, Fowler K, et al. Laterality and location influence catamenial seizure expression in women with partial epilepsy.
Neurology 2009;73:223–7.
15. Herzog A, Friedman M. Menstrual cycle interval and ovulation in
women with localization-related epilepsy. Neurology 2001;57:2133–5.
16. Bonuccelli U, Melis G, Paoletti A, et al. Unbalanced progesterone
and estradiol secretion in catamenial epilepsy. Epilepsy Res 1989;
3:100–6.
17. Kumar N, Behari M, Ahuja G, et al. Phenytoin levels in catamenial
epilepsy. Epilepsia 1988;29:155–8.
18. Feely M, Calvert R, Gibson J. Clobazam in catamenial epilepsy. A
model for evaluating anticonvulsants. Lancet 1982;2:71–3.
19. Gilad R, Sadeh M, Rapoport A, et al. Lamotrigine and catamenial
epilepsy. Seizure 2008;17:531–4.