Menstrual Related Epilepsy

1. Ade Wijaya, MD – August 2018

2.  Introduction
 Pathophysiology
 Patterns
 Hormonal effcts on epilepsy
 Treatment
 Summary

3.  Seizures tend to occur in cluster (50%)
 Periodicity of seizure exacerbation aligns
with the menstrual cycle  Catamenial
Epilepsy
Taubøll E, Lundervold A, Gjerstad L. Temporal distribution of seizures in epilepsy. Epilepsy Res 1991;8(2):153–65.
Herzog AG, Fowler KM, Sperling MR, Massaro JM3; Progesterone Trial Study Group. Distribution of seizures across the menstrual cycle in women with
epilepsy. Epilepsia 2015;56(5):58–62.
Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997;38(10):1082–8

4.  Catamenial epilepsy is likely attributable to
1) neuroactive properties of reproductive
steroid hormones,
2) cyclic variation in their serum levels,
3) susceptibility of epileptic foci to effects of
neuroactive steroids.
Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997;38(10):1082–8

5. Perimenstrual
LutealPeriovulatory
Herzog AG, Fowler KM, Sperling MR, Massaro JM3; Progesterone Trial Study Group. Distribution of seizures across the menstrual cycle in women with
epilepsy. Epilepsia 2015;56(5):58–62.
Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997;38(10):1082–8
Herzog AG, Harden CL, Liporace J, Pennell P, Schomer DL, Sperling M, et al. Frequency of catamenial seizure exacerbation in women with localization
related epilepsy. Ann Neurol 2004;56(3):431–4.

6. Herzog AG, Fowler KM, Sperling MR, Massaro JM3; Progesterone Trial Study Group. Distribution of seizures across the menstrual cycle in women with
epilepsy. Epilepsia 2015;56(5):58–62.
Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997;38(10):1082–8
Herzog AG, Harden CL, Liporace J, Pennell P, Schomer DL, Sperling M, et al. Frequency of catamenial seizure exacerbation in women with localization
related epilepsy. Ann Neurol 2004;56(3):431–4.

7.  Estradiol  Neuroexcitatory effects that can
lower seizure thresholds.
 Progesterone 
- Membrane-mediated inhibitory effects by
potentiating GABAA-mediated chloride
conductance
- Potentiates action of the powerful
endogenous inhibitory substance adenosine,
- Diminishes nicotinic acetylcholine receptor-
mediated conductance.
Herzog AG., Current Concepts of Catamenial Epilepsy. Epilepsi 2016;22(3):75-85

8.  AP and allo-THDOC hyperpolarize
hippocampal and other neurons by
potentiating GABAA-mediated inhibition 
anticonvulsant effect
 Pregnenolone sulfate and
dehydroepiandrosterone sulfate (DHEAS)
increase neuronal firing when directly
applied to neurons by negatively modulating
the GABAA receptor and by facilitating
glutamate-induced excitation at the NMDA
receptor
Paul SM, Purdy RH. Neuroactive steroids. FASEB J 1992;6:2311–22.
Gee KW, McCauley LD, Lan NC. A putative receptor for neurosteroids on the GABAA receptor complex: the pharmacological properties
and therapeutic potential of epalons. Crit Rev Neurobiol 1995;9(2-3):207–27.
Irwin RP, Maragakis NJ, Rogawski MA, Purdy RH, Farb DH, Paul SM. Pregnenolone sulfate augments NMDA receptor mediated increases in intracellular Ca2+
in cultured rat hippocampal neurons. Neurosci Lett 1992;141(1):30–4.

9. Herzog AG., Current Concepts of Catamenial Epilepsy. Epilepsi 2016;22(3):75-85

10.  Progestine therapy
 GnRH analogue

11.  Seizures usually occur in cluster
 Menstrual cycle related  catamenial epilepsy
 Estradiol  excitatory vs Progesterone  inhibitory
 Treatment: progesterone and its derivates