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Doodipala Samba Reddy - One of the best experts on this subject based on the ideXlab platform.
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Catamenial-like seizure exacerbation in mice with targeted ablation of extrasynaptic δGABA-a receptors in the brain.
Journal of neuroscience research, 2017Co-Authors: Bryan L. Clossen, Doodipala Samba ReddyAbstract:Neurosteroids play a key role in Catamenial Epilepsy, a menstrual cycle-related seizure clustering in women with Epilepsy. While neurosteroids act on all GABA-A receptor isoforms, they cause greater effects on extrasynaptic δGABA-A receptors that mediate tonic inhibition in the brain. Previously, we identified a potential GABA-A receptor mechanism for Catamenial Epilepsy. However, the precise functional role of extrasynaptic δGABA-A receptors in the pathophysiology of Catamenial Epilepsy remains unclear. In this study, we utilized mice lacking extrasynaptic δGABA-A receptors (δKO) to investigate whether reduction of tonic inhibition affects Catamenial seizure susceptibility or intensity. Intact female wildtype (WT) and δKO mice were subjected to hippocampus kindling until they exhibited stage 5 seizures. Elevated gonadal hormone-based neurosteroid levels were induced by standard gonadotropin regimen and neurosteroid withdrawal (NSW) was triggered by finasteride. NSW increased susceptibility to, as well the intensity of evoked Catamenial-like seizures in WT and δKO mice. However, fully kindled δKO mice exhibited an accelerated and augmented response to NSW, with a more rapid increase in seizure susceptibility and intensity than WT mice undergoing the NSW paradigm. Moreover, δKO mice in NSW showed reduced benzodiazepine sensitivity, but in stark contrast to the increased neurosteroid sensitivity observed in WT animals, δKO mice displayed no change in neurosteroid sensitivity in response to NSW. The increased Catamenial seizure exacerbation and alterations in antiseizure drug responses are consistent with NSW-induced changes in the abundance of δGABA-A receptors. Collectively, these findings provide evidence of a potential protective role for extrasynaptic δGABA-A receptors in Catamenial-like seizures. © 2017 Wiley Periodicals, Inc.
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Perimenstrual Seizures and Neurosteroid Withdrawal
Models of Seizures and Epilepsy, 2017Co-Authors: Doodipala Samba ReddyAbstract:Abstract Catamenial Epilepsy is a gender-specific condition in which epileptic seizures are clustered most often around perimenstrual or periovulatory period. Perimenstrual seizure exacerbation is thought to be due to neurosteroid withdrawal at the time of menstruation. A few rodent paradigms are designed to model neurosteroid withdrawal and perimenstrual seizures. The validation is mostly based on responses to antiepileptic drugs and neurosteroid sensitivity. These rodent models are helpful to define the molecular mechanisms of perimenstrual seizures and to screen new therapeutic agents for the treatment or prevention of Catamenial seizures.
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Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy
Frontiers in cellular neuroscience, 2016Co-Authors: Doodipala Samba ReddyAbstract:Catamenial Epilepsy is a type of refractory Epilepsy characterized by seizure clusters around perimenstrual or periovulatory period. The pathophysiology of Catamenial Epilepsy still remains unclear, yet there are few animal models to study this gender-specific disorder. The pathophysiology of perimenstrual Catamenial Epilepsy involves the withdrawal of the progesterone-derived GABAergic neurosteroids due to the decline in progesterone level at the time of menstruation. These manifestations can be faithfully reproduced in rodents by specific neuroendocrine manipulations. Since mice and rats, like humans, have ovarian cycles with circulating hormones, they appear to be suitable animal models for studies of perimenstrual seizures. Recently, we created specific experimental models to mimic perimenstrual seizures. Studies in rat and mouse models of Catamenial Epilepsy show enhanced susceptibility to seizures or increased seizure exacerbations following neurosteroid withdrawal. During such a seizure exacerbation period, there is a striking decrease in the anticonvulsant effect of commonly prescribed antiepileptics, such as benzodiazepines, but an increase in the anticonvulsant potency of exogenous neurosteroids. We discovered an extrasynaptic molecular mechanism of Catamenial Epilepsy. In essence, extrasynaptic δGABA-A receptors are upregulated during perimenstrual-like neuroendocrine milieu. Consequently, there is enhanced antiseizure efficacy of neurosteroids in Catamenial models because δGABA-A receptors confer neurosteroid sensitivity and greater seizure protection. Molecular mechanisms such as these offer a strong rationale for the clinical development of a neurosteroid replacement therapy for Catamenial Epilepsy.
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Neurosteroids and Their Role in Sex-Specific Epilepsies
Neurobiology of Disease, 2014Co-Authors: Doodipala Samba ReddyAbstract: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 αγδ-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.
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a mouse kindling model of perimenstrual Catamenial Epilepsy
Journal of Pharmacology and Experimental Therapeutics, 2012Co-Authors: Doodipala Samba Reddy, Jordan Gould, Omkaram GangisettyAbstract:Catamenial Epilepsy is caused by fluctuations in progesterone-derived GABAA 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 GABAA 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 α4 and δ subunits of GABAA 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 GABAA 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.
Andrew G. Herzog - One of the best experts on this subject based on the ideXlab platform.
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Hormonal therapies: progesterone.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2009Co-Authors: Andrew G. HerzogAbstract:Seizures do not occur randomly in the majority of people with Epilepsy. They tend to cluster. Seizure clusters, in turn, commonly occur with a temporal rhythmicity that shows a readily identifiable and predictable periodicity. When the periodicity of seizure exacerbation in women conforms to that of the menstrual cycle, it is commonly known as Catamenial Epilepsy. This may be attributable to 1) the neuroactive properties of steroid hormones and 2) the cyclic variation in their serum levels. If hormones play a role in seizure occurrence, hormones may also have a role in treatment. Progesterone has potent GABAergic metabolites that may provide safe and effective seizure control in women who have Catamenial Epilepsy.
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Circalunar and ultralunar periodicities in women with partial seizures.
Epilepsia, 2008Co-Authors: Mark Quigg, Kristen M Fowler, Andrew G. HerzogAbstract:PURPOSE Little consensus exists for the definition of Catamenial Epilepsy. Few studies have evaluated the periodicity of seizures to test the hypothesis that seizures in women have periodic patterns of occurrence independent of a priori hormonal considerations. In the present study, we determined seizure periodicity according to a "menstrual clock" provided by a common phase marker of the onset of menses. METHODS Seizure and menstrual diaries of approximately 3 months duration were obtained from women enrolled in a trial of hormonal therapy for localization-related Epilepsy. Midluteal progesterone levels identified ovulatory (>or=5 ng/ml, OC) from anovulatory cycles (AC). Individual cycles were normalized to a common phase and period (day 0 = menses onset, intervening days = 28 bins). Periodicity of combined data was estimated with cosinor-nonlinear least squares analysis. Best-fit rhythms were estimated with 95% confidence limits. RESULTS 100 patients provided 3344 seizures within 293 cycles (77% OC, 20% AC, indeterminate 3%). OC seizures displayed a circalunar rhythm with peak phase of occurrence at onset of menses. AC seizures also featured a circalunar rhythm that peaked at menses onset but also had ultralunar rhythms of approximately 14 and approximately 9 days. DISCUSSION Seizures in women with Epilepsy occur in circalunar rhythms. OC and AC seizures differ in seizure timing with the latter occurring in ultralunar rhythms in addition to the predominant circalunar rhythm. This finding supports the existence of Catamenial Epilepsy and differences in patterns of seizure occurrence between OC and AC.
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Sensitivity and specificity of the association between Catamenial seizure patterns and ovulation.
Neurology, 2008Co-Authors: Andrew G. Herzog, Kristen M FowlerAbstract:Some ovarian steroids such as estradiol (E)1,2 and progesterone (P)3,4 have neuroactive properties that can affect neuronal excitability. Cyclic changes in the serum concentrations of these steroids in relation to the menstrual cycle may induce variation in seizure frequency that has been termed Catamenial Epilepsy.5,6 There is statistical evidence to support the existence of at least three patterns: 1) perimenstrual (C1: day −3 to 3), 2) periovulatory (C2: day 10 to −13) in ovulatory cycles, and 3) luteal (C3: day 10 to 3) in anovulatory cycles. Day 1 refers to the day of onset of menstrual flow and Day −14 is presumed to represent the day of ovulation in ovulatory cycles.5,6 There are also mathematically based levels of seizure exacerbation for designation of Catamenial Epilepsy for each of these patterns. Although different patterns of Catamenial exacerbation have been observed with ovulatory and anovulatory cycles, their sensitivity and specificity remain to be established.5,6 ### Methods. The subjects were 100 women with localization-related Epilepsy, 13 to 45 years of age, who had intractable seizures, i.e., persistence of two or more monthly seizures despite documented trials of at least two antiepileptic drugs with therapeutic range levels. The subjects were participating in the baseline phase of a clinical trial of progesterone therapy. The women recorded …
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Catamenial Epilepsy: definition, prevalence pathophysiology and treatment.
Seizure, 2008Co-Authors: Andrew G. HerzogAbstract:Seizures do not occur randomly. They tend to cluster in the majority of men and women with Epilepsy. Seizure clusters, in turn, often show a periodicity. When the periodicity of seizure exacerbation aligns itself with that of the menstrual cycle, it is designated as Catamenial Epilepsy. The neuroactive properties of reproductive steroids and the cyclic variation in their serum concentrations are important pathophysiologic factors. Recent investigations have demonstrated and confirmed the existence of at least three patterns of Catamenial seizure exacerbation: perimenstrual and periovulatory in ovulatory cycles and entire luteal phase in anovulatory cycles. A rational mathematical basis for the categorization of seizure exacerbation as Catamenial Epilepsy has been developed. It identifies approximately one third of women as having Catamenial Epilepsy. If seizures show hormonal sensitivity in their occurrence, they may also respond to hormonal treatment. Successful open label trials using cyclic natural progesterone supplement, depomedroxyprogesterone and gonadotropin-releasing hormone analogues in women and using testosterone with or without aromatase inhibitor in men have been reported. Prospective, randomized, placebo-controlled, double-blind investigations are warranted and under way.
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frequency of Catamenial seizure exacerbation in women with localization related Epilepsy
Annals of Neurology, 2004Co-Authors: Andrew G. Herzog, Cynthia L Harden, Joyce Liporace, Page B Pennell, Donald L Schomer, Michael R Sperling, Kristen M Fowler, Blagovast Nikolov, Sevie Shuman, Melanee NewmanAbstract:This investigation assessed the frequency of Catamenial Epilepsy in 87 women who charted seizures and menses during three cycles. Catamenial Epilepsy designation was made if two of three cycles showed at least one of three previously defined Catamenial patterns. Among ovulatory cycles, average daily seizure frequency was significantly greater during the perimenstrual and preovulatory phases. Among anovulatory cycles, average daily seizure frequency was substantially less during the midfollicular phase than during the remainder of the cycle. Overall, 39.1% of the women had Catamenial Epilepsy.
Michael A. Rogawski - One of the best experts on this subject based on the ideXlab platform.
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Neurosteroid Replacement Therapy for Catamenial Epilepsy
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2009Co-Authors: Doodipala Samba Reddy, Michael A. RogawskiAbstract:Perimenstrual Catamenial Epilepsy, the cyclical occurrence of seizure exacerbations near the time of menstruation, affects a high proportion of women of reproductive age with drug-refractory Epilepsy. Enhanced seizure susceptibility in perimenstrual Catamenial Epilepsy is believed to be due to the withdrawal of the progesterone-derived GABAA receptor modulating neurosteroid allopregnanolone as a result of the fall in progesterone at the time of menstruation. Studies in a rat pseudopregnancy model of Catamenial Epilepsy indicate that after neurosteroid withdrawal there is enhanced susceptibility to chemoconvulsant seizures. There is also a transitory increase in the frequency of spontaneous seizures in epileptic rats that had experienced pilocarpine-induced status epilepticus. In the Catamenial Epilepsy model, there is a marked reduction in the antiseizure potency of anticonvulsant drugs, including benzodiazepines and valproate, but an increase in the anticonvulsant potency and protective index of neurosteroids such as allopregnanolone and the neurosteroid analog ganaxolone. The enhanced seizure susceptibility and benzodiazepine-resistance subsequent to neurosteroid withdrawal may be related to reduced expression and altered kinetics of synaptic GABAA receptors and increased expression of GABAA receptor subunits (such as α4) that confer benzodiazepine insensitivity. The enhanced potency of neurosteroids may be due to a relative increase after neurosteroid withdrawal in the expression of neurosteroid-sensitive δ-subunit-containing perisynaptic or extrasynaptic GABAA receptors. Positive allosteric modulatory neurosteroids and synthetic analogs such as ganaxolone may be administered to prevent Catamenial seizure exacerbations, in what we call neurosteroid replacement therapy.
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Neurosteroid withdrawal model of perimenstrual Catamenial Epilepsy.
Epilepsia, 2002Co-Authors: Doodipala Samba Reddy, Hee Yong Kim, Michael A. RogawskiAbstract:Summary: Purpose: Perimenstrual Catamenial Epilepsy, the increase in seizure frequency that some women with Epilepsy experience near the time of menstruation, may in part be related to withdrawal of the progesterone metabolite allopregnanolone, an endogenous anticonvulsant neurosteroid that is a potent positive allosteric γ-aminobutyric acidA (GABAA) receptor modulator. The objective of this study was to develop an animal model of perimenstrual Catamenial Epilepsy for use in evaluating drug-treatment strategies. Methods: A state of prolonged high serum progesterone (pseudopregnancy) was induced in 26-day-old female rats by sequential injection of pregnant mares' serum gonadotropin and human chorionic gonadotropin. Neurosteroid withdrawal was induced by treatment with finasteride (100 mg/kg, i.p.), a 5α-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone. Plasma progesterone and allopregnanolone levels were measured by gas chromatography/electron capture negative chemical ionization mass spectrometry. Seizure susceptibility was evaluated with the convulsant pentylenetetrazol (PTZ). Results: Plasma allopregnanolone levels were markedly increased during pseudopregnancy (peak level, 55.1 vs. control diestrous level, 9.3 ng/mL) and were reduced by 86% 24 h after finasteride treatment (6.4 ng/mL). Progesterone levels were unaffected by finasteride. After finasteride-induced withdrawal, rats showed increased susceptibility to PTZ seizures. There was a significant increase in the number of animals exhibiting clonic seizures when challenged with subcutaneous PTZ (60 mg/kg) compared with control pseudopregnant animals not undergoing withdrawal and nonpseudopregnant diestrous females. The CD50 (50% convulsant dose) was 46 mg/kg, compared with 73 mg/kg in nonwithdrawn pseudopregnant animals and 60 mg/kg in diestrous controls. The threshold doses for induction of various seizure signs, measured by constant intravenous infusion of PTZ, were reduced by 30–35% in neurosteroid-withdrawing animals compared with control diestrous females. No change in threshold was observed in pseudopregnant rats treated from days 7 to 11 with finasteride, demonstrating that high levels of progesterone alone do not alter seizure reactivity. Conclusions: Neurosteroid withdrawal in pseudopregnant rats results in enhanced seizure susceptibility, providing an animal model of perimenstrual Catamenial Epilepsy that can be used for the evaluation of new therapeutic approaches.
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Enhanced Anticonvulsant Activity of Neuroactive Steroids in a Rat Model of Catamenial Epilepsy
Epilepsia, 2002Co-Authors: Doodipala Samba Reddy, Michael A. RogawskiAbstract:Summary: Purpose: Perimenstrual Catamenial Epilepsy may in part be due to withdrawal of the endogenous progesterone-derived neurosteroid allopregnanolone that potentiates γ-aminobutyric acidA (GABAA) receptor–mediated inhibition. Here we sought to determine whether the anticonvulsant potencies of neuroactive steroids, benzodiazepines, phenobarbital (PB), and valproate (VPA) are altered during the heightened seizure susceptibility accompanying neurosteroid withdrawal in a rat model of perimenstrual Catamenial Epilepsy. Methods: Test drugs were evaluated for their ability to alter the convulsant activity of pentylenetetrazol (PTZ) in young adult female rats, in pseudopregnant rats with prolonged exposure to high levels of progesterone (and its neurosteroid metabolites), and in pseudopregnant rats 24 h after acute withdrawal of neurosteroids by treatment with the 5α-reductase inhibitor finasteride. Test drugs were administered at doses equivalent to twice their ED50 values for protection against PTZ-induced clonic seizures in naive young adult female rats. Results: The anticonvulsant activity of allopregnanolone (5 mg/kg, s.c.), pregnanolone (5 mg/kg, s.c.), allotetrahydrodeoxycorticosterone (15 mg/kg, s.c.), and tetrahydrodeoxycorticosterone (10 mg/kg, s.c.) were enhanced by 34–127% after neurosteroid withdrawal. The anticonvulsant activity of PB (65 mg/kg, i.p.) was also enhanced by 24% in neurosteroid-withdrawn animals. In contrast, the anticonvulsant activity of diazepam (4 mg/kg, i.p.), bretazenil (0.106 mg/kg, i.p.), and VPA (560 mg/kg, i.p.) were reduced or unchanged in neurosteroid-withdrawn animals. Conclusions: The anticonvulsant activity of neuroactive steroids is potentiated after neurosteroid withdrawal, supporting the use of such agents in the treatment of perimenstrual Catamenial Epilepsy.
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Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a rat model of Catamenial Epilepsy.
The Journal of pharmacology and experimental therapeutics, 2000Co-Authors: Doodipala Samba Reddy, Michael A. RogawskiAbstract:Perimenstrual Catamenial Epilepsy, the exacerbation of seizures in association with menstruation, may in part be due to withdrawal of the progesterone metabolite allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), an endogenous anticonvulsant neurosteroid that is a positive allosteric modulator of gamma-aminobutyric acid(A) receptors. Neurosteroid replacement is a potential approach to therapy, but natural neurosteroids have poor bioavailability and may be converted to metabolites with undesired progestational activity. The synthetic neuroactive steroid ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnane-20-one) is an orally active analog of allopregnanolone that is not converted to the hormonally active 3-keto form. To assess the potential of ganaxolone in the treatment of Catamenial seizure exacerbations, a state of persistently high serum progesterone (pseudopregnancy) was induced in 26-day-old female rats with gonadotropins, and neurosteroids were withdrawn on postnatal day 39 with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone. Finasteride treatment during pseudopregnancy results in a reduction in the threshold for pentylenetetrazol seizures. During this state of enhanced seizure susceptibility, there was a 3-fold increase in the anticonvulsant potency of ganaxolone (control ED(50) = 3.5 mg/kg; withdrawn = 1.2 mg/kg) without a change in the potency for induction of motor toxicity in the rotarod test. The plasma concentrations of ganaxolone did not differ significantly in control and withdrawn animals; the estimated plasma concentrations of ganaxolone producing 50% seizure protection were approximately 500 and approximately 225 ng/ml in control and withdrawn rats, respectively. Unlike ganaxolone, neurosteroid withdrawal was associated with a decrease in the anticonvulsant potency of diazepam (control ED(50) = 1.9 mg/kg; withdrawn = 4.1 mg/kg) and valproate (control ED(50) = 279 mg/kg; withdrawn = 460 mg/kg). The enhanced anticonvulsant potency of ganaxolone after neurosteroid withdrawal supports the use of ganaxolone as a specific treatment for perimenstrual Catamenial Epilepsy.
Kristen M Fowler - One of the best experts on this subject based on the ideXlab platform.
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Circalunar and ultralunar periodicities in women with partial seizures.
Epilepsia, 2008Co-Authors: Mark Quigg, Kristen M Fowler, Andrew G. HerzogAbstract:PURPOSE Little consensus exists for the definition of Catamenial Epilepsy. Few studies have evaluated the periodicity of seizures to test the hypothesis that seizures in women have periodic patterns of occurrence independent of a priori hormonal considerations. In the present study, we determined seizure periodicity according to a "menstrual clock" provided by a common phase marker of the onset of menses. METHODS Seizure and menstrual diaries of approximately 3 months duration were obtained from women enrolled in a trial of hormonal therapy for localization-related Epilepsy. Midluteal progesterone levels identified ovulatory (>or=5 ng/ml, OC) from anovulatory cycles (AC). Individual cycles were normalized to a common phase and period (day 0 = menses onset, intervening days = 28 bins). Periodicity of combined data was estimated with cosinor-nonlinear least squares analysis. Best-fit rhythms were estimated with 95% confidence limits. RESULTS 100 patients provided 3344 seizures within 293 cycles (77% OC, 20% AC, indeterminate 3%). OC seizures displayed a circalunar rhythm with peak phase of occurrence at onset of menses. AC seizures also featured a circalunar rhythm that peaked at menses onset but also had ultralunar rhythms of approximately 14 and approximately 9 days. DISCUSSION Seizures in women with Epilepsy occur in circalunar rhythms. OC and AC seizures differ in seizure timing with the latter occurring in ultralunar rhythms in addition to the predominant circalunar rhythm. This finding supports the existence of Catamenial Epilepsy and differences in patterns of seizure occurrence between OC and AC.
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Sensitivity and specificity of the association between Catamenial seizure patterns and ovulation.
Neurology, 2008Co-Authors: Andrew G. Herzog, Kristen M FowlerAbstract:Some ovarian steroids such as estradiol (E)1,2 and progesterone (P)3,4 have neuroactive properties that can affect neuronal excitability. Cyclic changes in the serum concentrations of these steroids in relation to the menstrual cycle may induce variation in seizure frequency that has been termed Catamenial Epilepsy.5,6 There is statistical evidence to support the existence of at least three patterns: 1) perimenstrual (C1: day −3 to 3), 2) periovulatory (C2: day 10 to −13) in ovulatory cycles, and 3) luteal (C3: day 10 to 3) in anovulatory cycles. Day 1 refers to the day of onset of menstrual flow and Day −14 is presumed to represent the day of ovulation in ovulatory cycles.5,6 There are also mathematically based levels of seizure exacerbation for designation of Catamenial Epilepsy for each of these patterns. Although different patterns of Catamenial exacerbation have been observed with ovulatory and anovulatory cycles, their sensitivity and specificity remain to be established.5,6 ### Methods. The subjects were 100 women with localization-related Epilepsy, 13 to 45 years of age, who had intractable seizures, i.e., persistence of two or more monthly seizures despite documented trials of at least two antiepileptic drugs with therapeutic range levels. The subjects were participating in the baseline phase of a clinical trial of progesterone therapy. The women recorded …
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frequency of Catamenial seizure exacerbation in women with localization related Epilepsy
Annals of Neurology, 2004Co-Authors: Andrew G. Herzog, Cynthia L Harden, Joyce Liporace, Page B Pennell, Donald L Schomer, Michael R Sperling, Kristen M Fowler, Blagovast Nikolov, Sevie Shuman, Melanee NewmanAbstract:This investigation assessed the frequency of Catamenial Epilepsy in 87 women who charted seizures and menses during three cycles. Catamenial Epilepsy designation was made if two of three cycles showed at least one of three previously defined Catamenial patterns. Among ovulatory cycles, average daily seizure frequency was significantly greater during the perimenstrual and preovulatory phases. Among anovulatory cycles, average daily seizure frequency was substantially less during the midfollicular phase than during the remainder of the cycle. Overall, 39.1% of the women had Catamenial Epilepsy.
Cynthia L Harden - One of the best experts on this subject based on the ideXlab platform.
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Gender issues in the neurobiology of Epilepsy: A clinical perspective
Neurobiology of Disease, 2014Co-Authors: Barbara S. Koppel, Cynthia L HardenAbstract:Abstract A patient's hormonal milieu contributes to the timing of emergence of several Epilepsy syndromes that are known to begin at puberty and recede with the end of reproductive potential. One's hormonal balance at any particular moment contributes to seizure occurrence in both men and women. The best studied condition, Catamenial Epilepsy, refers to seizure clusters occurring in a cyclical pattern related to menses. Treatment of Epilepsy using hormones complements standard antiepileptic therapy and its use will be reviewed, along with some other medications unique to Catamenial Epilepsy, such as diuretics. Seizures and “silent” epileptiform discharges in turn affect the hypothalamic pituitary axis and can cause release of hormones at inappropriate times leading to sexual dysfunction, menstrual irregularity, infertility and premature termination of reproductive states. Combined with psychological consequences of Epilepsy, this sexual dysfunction has deleterious effects on the quality of life in patients and their partners.
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frequency of Catamenial seizure exacerbation in women with localization related Epilepsy
Annals of Neurology, 2004Co-Authors: Andrew G. Herzog, Cynthia L Harden, Joyce Liporace, Page B Pennell, Donald L Schomer, Michael R Sperling, Kristen M Fowler, Blagovast Nikolov, Sevie Shuman, Melanee NewmanAbstract:This investigation assessed the frequency of Catamenial Epilepsy in 87 women who charted seizures and menses during three cycles. Catamenial Epilepsy designation was made if two of three cycles showed at least one of three previously defined Catamenial patterns. Among ovulatory cycles, average daily seizure frequency was significantly greater during the perimenstrual and preovulatory phases. Among anovulatory cycles, average daily seizure frequency was substantially less during the midfollicular phase than during the remainder of the cycle. Overall, 39.1% of the women had Catamenial Epilepsy.
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Hormones and seizures.
Cleveland Clinic Journal of Medicine, 2004Co-Authors: Nancy Foldvary-schaefer, Andrew G. Herzog, Cynthia L Harden, Tommaso FalconeAbstract:The opposing effects of estrogen (proconvulsant) and progesterone (anticonvulsant) on seizure threshold have been noted in animal and human studies. Levels of these hormones fluctuate throughout the menstrual cycle, and, in some women with Epilepsy, these fluctuations may be related to the occurrence of seizures around the time of menses or an increase in seizures in relation to the menstrual cycle, also known as Catamenial Epilepsy. Variations in concentrations of antiepileptic drugs across the menstrual cycle may also contribute to increased seizure susceptibility. Diagnosis of Catamenial Epilepsy requires careful assessment of menstrual and seizure diaries and characterization of cycle duration and type. While there are several approaches to the treatment of Catamenial Epilepsy, each is based on small, unblinded studies or anecdotal reports. It is important for the physician to work closely with the patient to determine whether her seizures are indeed Catamenial and to design an appropriate treatment plan.