Menstrual cycle worsening of epileptic seizures in women with symptomatic focal epilepsy

Bazán, Ana Carolina Belini; Montenegro, Maria Augusta; Cendes, Fernando; Li, Min; Guerreiro, Carlos A. M.

doi:10.1590/s0004-282x2005000500006

Cited by 37 publications

(19 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Epilepsy affects an estimated 1.3 million women in the United States (Kaplan et al, 2007; Pennell, 2008). Catamenial epilepsy affects from 10 – 70% of women with epilepsy (Herzog et al, 2004; Bazan et al, 2005; Gilad et al, 2008; Reddy, 2009; 2013b). The large variation in prevalence of catamenial epilepsy is partly because of methodological differences such as the criteria used for defining seizure exacerbation in relation to menstrual cycle, patients‘ self-reporting, diaries, and other records of seizures relating to menses.…”

Section: Catamenial Epilepsymentioning

confidence: 99%

Neurosteroids and their role in sex-specific epilepsies

Reddy

2014

Neurobiology of Disease

View full text Add to dashboard Cite

Neurosteroids are involved in sex-specific epilepsies. Allopregnanolone and related endogenous neurosteroids in the brain control excessive neuronal excitability and seizure susceptibility. Neurosteroids activate GABA-A receptors, especially extrasynaptic αβδ-GABA-A receptor subtypes that mediate tonic inhibition and thus dampen network excitability. Our studies over the past decade have shown that neurosteroids are broad-spectrum anticonvulsants and confer seizure protection in various animal models. Neurosteroids also exert antiepileptogenic effects. There is emerging evidence on a critical role for neurosteroids in the pathophysiology of the sex-specific forms of epilepsies such as catamenial epilepsy, a menstrual cycle-related seizure disorder in women. Catamenial epilepsy is a neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around the perimenstrual or periovulatory period. Apart from ovarian hormones, fluctuations in neurosteroid levels could play a critical role in this gender-specific epilepsy. Neurosteroids also regulate the plasticity of synaptic and extrasynaptic GABA-A receptors in the hippocampus and other regions involved in epilepsy pathology. Based on these studies, we proposed a neurosteroid replacement therapy for catamenial epilepsy. Thus, neurosteroids are novel drug targets for pharmacotherapy of epilepsy.

show abstract

Section: Catamenial Epilepsymentioning

confidence: 99%

Neurosteroids and their role in sex-specific epilepsies

Reddy

2014

Neurobiology of Disease

View full text Add to dashboard Cite

show abstract

“…There are about 1.5 million women of child-bearing age with epilepsy in the United States; catamenial seizure exacerbations affect up to 70% of these women (Herzog et al, 2004; Bazan et al, 2005; Quigg et al, 2009; Reddy, 2009a; Kim et al, 2010; Verrotti et al, 2010). Although there are several forms of catamenial epilepsy, neurosteroids have been implicated only in the seizure exacerbations that occur in the most common situation, which is when women with normal menstrual cycles experience seizure exacerbations in the perimenstrual period.…”

Section: Role Of Endogenous Neurosteroids In Epilepsymentioning

confidence: 99%

Role of Anticonvulsant and Antiepileptogenic Neurosteroids in the Pathophysiology and Treatment of Epilepsy

Reddy¹

2011

Front. Endocrin.

View full text Add to dashboard Cite

This review highlights the role of major endogenous neurosteroids in seizure disorders and the promise of neurosteroid replacement therapy in epilepsy. Neurosteroids are endogenous modulators of seizure susceptibility. Neurosteroids such as allopregnanolone (3α-hydroxy-5α-pregnane-20-one) and allotetrahydrodeoxycorticosterone (3α,21-dihydroxy-5α-pregnan-20-one) are positive modulators of GABA-A receptors. Aside from peripheral tissues, neurosteroids are synthesized within the brain, mostly in principal neurons. Neurosteroids potentiate synaptic GABA-A receptor function and also activate δ-subunit-containing extrasynaptic GABA-A receptors that mediate tonic currents and thus may play an important role in neuronal network excitability and seizure susceptibility. Our studies over the past decade have shown that neurosteroids are broad-spectrum anticonvulsants and confer seizure protection in various animal models. They protect against seizures induced by GABA-A receptor antagonists, 6-Hz model, pilocarpine-induced limbic seizures, and seizures in kindled animals. Unlike benzodiazepines, tolerance does not occur to their actions during chronic administration. Our recent studies provide compelling evidence that neurosteroids may have antiepileptogenic properties. There is emerging evidence that endogenous neurosteroids may play a key role in the pathophysiology of catamenial epilepsy, stress–sensitive seizure conditions, temporal lobe epilepsy, and alcohol-withdrawal seizures. It is suggested that neurosteroid replacement with natural or synthetic neurosteroids may be useful in the treatment of epilepsy. Synthetic analogs of neurosteroids that are devoid of hormonal side effects show promise in the treatment of diverse seizure disorders. Agents that stimulate endogenous production of neurosteroids may also be useful for treatment of epilepsy.

show abstract

“…The word "catamenial" is derived from the Greek word "katamenios" meaning monthly. Catamenial seizure exacerbations are reported to affect up to 70% of women with epilepsy (Herzog et al, 2004;Bazá n et al, 2005;Quigg et al, 2009). There are three forms of catamenial epilepsy: perimenstrual and periovulatory in normal cycles and luteal in inadequate lutealphase cycles (Herzog et al, 1997.…”

Section: Introductionmentioning

confidence: 99%

A Mouse Kindling Model of Perimenstrual Catamenial Epilepsy

Reddy

Gould²,

Gangisetty³

2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Catamenial epilepsy is caused by fluctuations in progesteronederived GABA A receptor-modulating anticonvulsant neurosteroids, such as allopregnanolone, that play a significant role in the pathophysiology of epilepsy. However, there is no specific mouse model of catamenial epilepsy. In this study, we developed and characterized a mouse model of catamenial epilepsy by using the neurosteroid-withdrawal paradigm. It is hypothesized that seizure susceptibility decreases when neurosteroid levels are high (midluteal phase) and increases during their withdrawal (perimenstrual periods) in close association with GABA A receptor plasticity. A chronic seizure condition was created by using the hippocampus kindling model in female mice. Elevated neurosteroid levels were induced by sequential gonadotropin treatment, and withdrawal was induced by the neurosteroid synthesis inhibitor finasteride. Elevated neurosteroid exposure reduced seizure expression in fully kindled mice. Fully kindled mice subjected to neurosteroid withdrawal showed increased generalized seizure frequency and intensity and enhanced seizure susceptibility. They also showed reduced benzodiazepine sensitivity and enhanced neurosteroid potency, similar to the clinical catamenial seizure phenotype. The increased susceptibility to seizures and alterations in antiseizure drug responses are associated with increased abundance of the ␣4 and ␦ subunits of GABA A receptors in the hippocampus. These findings demonstrate that endogenous neurosteroids protect against seizure susceptibility and their withdrawal, such as that which occurs during menstruation, leads to exacerbation of seizure activity. This is possibly caused by specific changes in GABA A receptor-subunit plasticity and function, therefore providing a novel mouse model of human perimenstrual catamenial epilepsy that can be used for the investigation of disease mechanisms and new therapeutic approaches.

show abstract

Menstrual cycle worsening of epileptic seizures in women with symptomatic focal epilepsy

Cited by 37 publications

References 23 publications

Neurosteroids and their role in sex-specific epilepsies

Neurosteroids and their role in sex-specific epilepsies

Role of Anticonvulsant and Antiepileptogenic Neurosteroids in the Pathophysiology and Treatment of Epilepsy

A Mouse Kindling Model of Perimenstrual Catamenial Epilepsy

Contact Info

Product

Resources

About