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Catamenial Epilepsy: In Search of a Clinical Entity and Its Prevalence.

Abstract: The prevalence of catamenial epilepsy has been difficult to determine for several reasons, including menstrual cycle variability and randomness of seizure occurrence, a high prevalence of seizure clustering in males and nonmenstruating females with epilepsy, and the lack of a definition of catamenial epilepsy in previous studies. Recently, a definition describing three distinct patterns that may provide a sensible nomenclature for future research on catamenial epilepsy has been proposed, and it may provide standardized criteria for inclusion in catamenial epilepsy studies. Such a definition should allow estimates of true prevalence of this disorder to be more precise and prospective treatment trials to be designed.

A pattern of predominant seizure occurrence or exacerbation of seizure frequency in temporal relationship to the menstrual cycle is referred to as catamenial epilepsy. Catamenial epilepsy was first examined by Gowers in 1885 (as cited in Newmark and Penry[11]) and Locock in 1857 (as cited in Bandler, Kaufman, Dykens, Schleifer and Shapiro[3]). The recent focus on women's health has resulted in an increased awareness of catamenial epilepsy. The Epilepsy Foundation has promoted the Women and Epilepsy Initiative to stimulate research on catamenial epilepsy and other concerns unique to women with epilepsy, offering new hope to women with seizures.

Although the existence of catamenial epilepsy is generally accepted, uncertainty about its prevalence remains. A chronological review of studies investigating the prevalence of catamenial epilepsy is presented, outlining the progress made in understanding catamenial epilepsy and suggesting potential directions for future research. Investigators' varying definitions of catamenial epilepsy and the potential impact on their conclusions about the prevalence of catamenial epilepsy are given particular consideration. This article reviews the literature on catamenial epilepsy and the struggle to create a uniform acceptable definition for the condition. Implications for further research and nursing care are discussed.

Review of the Literature

Most investigations relied solely on women's diaries,[1,14] or medical records[5,9] that recorded both seizures and menses. Some studies also attempted to determine ovulatory state of the menstrual cycles[2,3,8] to explore possible differences between ovulatory and anovulatory cycles and to examine different types of catamenial patterns.

In 1928 Healey reported on 73 women with epilepsy, 53 of whom were menstruating.[7] Five of the 53 women had seizures "at" menstruation only, and 40 had increased seizure frequency "at" menstruation. He observed a high percentage of dysmenorrhea in 22 of the 53 women. Unfortunately, this study is of uncertain utility because no information on patient inclusion/exclusion criteria, patient setting, seizure type, cause of epilepsy, or study methodology was described.

Dickerson[5] and Laidlaw[9] independently studied large numbers of institutionalized women for extended follow-up, reaching opposite conclusions on the prevalence of catamenial epilepsy. Dickerson reviewed the charts of 269 menstruating women in a state hospital for epilepsy for one calendar year. Etiologies and types of seizures were not specified. No significant correlation between menses and seizure frequency was detected, although a high incidence of irregular menses may have skewed the results. Of the 269 women, 33 (12.3%) had no seizures during menses. No women had seizures exclusively with menses. Only 27 women (10%) showed an increased number of seizures at the "approach of the menstrual period."

Laidlaw[9] retrospectively reviewed the records over a 25-year period on menstruating women residing in an institution for individuals with epilepsy. A total of 50 women with 9,293 menstrual cycles and 33,468 seizures during 939 patient years were analyzed. Only patients with regular menstrual cycles were included. Types of seizures were not described. Of the 50 women, 72% showed an increase in seizures immediately before, during, or after menses.

In a prospective study by Ansell and Clarke,[1] 42 outpatients recorded menses and seizures for 2-4 months. Sixty-three percent recorded more seizures either during menses or the 24 hours before menses. No difference was noted between idiopathic and symptomatic epilepsy, but seizure types were not described. No comment was made about the regularity of menses.

A study by Bandler et al.[3] was the first to document the time of ovulation and seizure frequency in different phases of the menstrual cycle. They studied 29 women of normal intelligence for 3 years, including 6-39 menstrual cycles. All seizure types of both idiopathic and symptomatic epilepsy were included, but subgroup analysis of different seizure types and etiologies was not performed. The women recorded seizures and menses in their diaries. Daily vaginal smears were taken and daily basal temperatures recorded. Twenty-three of the women ovulated during each menstrual cycle, and the other six ovulated in at least half of the cycles. Interestingly, although 57% of the women thought they had catamenial epilepsy, seizures occurred randomly throughout the menstrual cycles without any particular phase preference. In some of the women, seizures tended to occur only in a particular phase of the menstrual cycle, but this varied among individual patients.

In recent years, more sophisticated hormonal analysis has become feasible. Backstrom[2] measured progesterone and estrogen levels and investigated whether there was a relationship with seizure frequency. Backstrom studied nine menstrual cycles in seven women with frequent seizures to determine Whether there was a correlation between hormonal levels and seizure frequency. These women were chosen for the study because of their high frequency of seizures; no other criteria were used. The women kept accurate calendars on which they recorded their menstrual cycles and seizures. Every other day measurements of progesterone and estrogen levels were obtained. Six of the women's menstrual cycles were ovulatory and three were anovulatory. The investigation found that in the ovulatory cycles there were more seizures when the estrogen/progesterone ratio was low during the luteal phase. In the three anovulatory cycles, the progesterone level remained low throughout the menstrual cycle and estrogen levels fluctuated, suggesting that seizures increased in frequency when estrogen levels were high. Thus, Backstrom noticed two peak times of increased seizure frequency--at the beginning of menses and at the time of ovulation.

Tauboll, Lundervold, and Gjerstad[14] examined the temporal distribution of seizures in 16 volunteers in a study of factors affecting seizure occurrence. These individuals were followed prospectively with seizure diaries. A total of 3,229 seizures were recorded over 19.7 patient years. There were nine women with idiopathic epilepsy in the study, and a total of 90 menstrual cycles were recorded. Seven (78%) of the nine women had a relationship between their menstrual cycles and seizure occurrences. Six of the seven women had an increase in seizures during menses, and one of the seven women had premenstrually increased seizures. The median increase in seizures for these women was 63%. However, in 11 of the 16 individuals of both sexes, seizures did not occur randomly, indicating that in epileptic patients independent of sex, seizures often follow a pattern. The authors' conclusion was that although there often is an apparent correlation between menstrual cycles and seizures, this may represent a nonhormonal phenomenon of seizure clustering, because a similar nonrandom seizure pattern occurred in the male patients as well.

These older studies are limited by their failure to adequately define catamenial epilepsy. Broadly, catamenial epilepsy may refer to seizures that occur in association with menses, but whether study designs include seizures occurring exclusively during menses or premenstrual days as well varied in these studies. The number of days included as premenstrual and menstrual is also not uniformly defined in most studies. Healey[7] vaguely referred to catamenial epilepsy as seizures occurring "at menses." Dickerson[5] described catamenial epilepsy as increased seizure frequency "as menses is approaching" and "at onset of menses," with seizures declining in frequency as the period "progresses." Laidlaw[9] defined catamenial epilepsy as an increased seizure frequency immediately before, during, or after menses.

Ansell and Clarke[1] were more precise, characterizing catamenial epilepsy as an increase in seizure frequency during menses and the 24 hours preceding menses. Tauboll, Lundervold, and Gjerstad[14] attempted to further refine the time frame and described catamenial epilepsy as increased seizure frequency within the four days prior to menses and the first five days of menses.

Also lacking in many of these studies is a precise definition of the degree of seizure exacerbation required to qualify as catamenial epilepsy. Most of the investigators considered catamenial epilepsy to be present if there were any increase in seizures catamenially compared to other times of the month.[1,2,3,5,7,9,14]

To circumvent these problems, Duncan, Read, and Brodie[6] employed a strict definition of catamenial epilepsy in their prospective study examining 40 consecutive women with intractable epilepsy. Antiepileptic drug levels were randomly measured to ensure that compliance or fluctuating drug levels did not influence seizure frequency. Catamenial epilepsy was defined as the occurrence of at least 75% of the seizures each month in a 10-day time frame that included 4 days preceding and 6 days following the start of menses. With this definition, only five (12.5%) out of 40 women had catamenial epilepsy. Of the five women with catamenial epilepsy, three had seizures exclusively during the 10-day time frame. The other two women with catamenial epilepsy had 85% and 91% of their seizures during the 10-day time frame. This study did not determine whether ovulation occurred, but six women with irregular menstrual cycles did not have catamenial epilepsy by their definition. Of the 40 women included in the study, 31 (78%) believed they had catamenial epilepsy, when in actuality only five women (12.5%) met the study's rigorously defined criteria for having catamenial epilepsy.

Herzog, Klein, and Ransil[8] also recognized the importance of a precise definition of catamenial epilepsy. In this study, 184 women consecutively referred for intractable epilepsy were followed through one menstrual cycle. The menstrual cycle was divided into four phases: menstrual, follicular, ovulatory, and luteal. The menstrual phase included the 3 days prior to menses and the first 3 days of menses. The follicular phase was defined as days 4 through 9. The ovulatory phase began on the 10th day after menses and continued through the 13th day prior to the next menses. The luteal phase was defined as 12 to 4 days prior to menses. Ovulation was considered to occur 14 days prior to menses. Progesterone level was measured on day 22 of the menstrual cycle to determine the presence of an inadequate luteal phase. Inadequate luteal phase referred to an abnormally low progesterone level during the second half of the menstrual cycle.

The results of the study supported three patterns of catamenial epilepsy. In ovulatory cycles two patterns were identified: perimenstrual seizure exacerbation (C1 pattern) and periovulatory exacerbation (C2 pattern). In the C1 pattern there were more seizures in the menstrual phase than in the follicular and luteal phases. In the C2 pattern there were more seizures in the ovulatory phase than in the follicular and luteal phases. The third pattern (C3) occurred in inadequate luteal phase cycles, and more seizures occurred in the ovulatory, luteal, and menstrual phases than during the follicular phase. Of the 98 women who had ovulatory cycles, 70 (71.4%) had a catamenial pattern to their seizures. Of the 70 women with catamenial epilepsy, 67 (95.7%) were found to have both C1 and C2 patterns, and 3 (4.3%) showed a C1 pattern only. Of the 86 women found to have inadequate luteal phase cycles, 67 (77.9%) demonstrated a C3 pattern of seizure exacerbation and only 10 (11.6%) showed pattern C1 or C2.

Herzog, Klein, and Ransil[8] recommended that at least a twofold increase in seizure frequency be used to identify catamenial epilepsy. Based on this criterion, approximately one-third of the women in their study were found to have catamenial epilepsy. No differences in catamenial patterns were noted when complex partial seizures were compared with secondarily generalized seizures. No significant differences were noted in antiepileptic drugs.

Nursing Implications

Knowledge of catamenial epilepsy is important for nurses caring for women with epilepsy. With this knowledge, nurses can discuss catamenial patterns that women patients with epilepsy may observe and assist other women in recording menses and seizures in order to look for catamenial patterns. By observing a catamenial pattern of seizures in patients, nurses can help women prepare in advance for the time of the month they are more likely to experience seizures. Recognition of catamenial epilepsy will allow nurses to identify women for whom specific treatments may be helpful. These treatments may include hormonal therapy, additional medication, or an increased dose of antiepileptic medication during catamenial exacerbation of seizures.[10] Because of the close working relationship with their patients, nurses are in an excellent position to further study catamenial epilepsy and to encourage women patients to consider participating in research investigating catamenial epilepsy.

Research Implications

Although catamenial epilepsy has been described for over a century, only recently have stringent criteria for defining catamenial epilepsy been advanced. A consistent, accurate and valid definition of catamenial epilepsy is needed in order to identify women with this condition before effective treatments can be developed.

Herzog, Klein, and Ransil propose a definition of catamenial epilepsy describing three patterns.[8] Population-based epidemiologic research replicating their patterns of catamenial epilepsy is needed for validation of this categorization. In addition, this study evaluated only single cycles in each patient, indicating the need for long-term follow-up studies to provide information on the consistency of patterns in women over time. More research is needed on changes in catamenial patterns as women go through menopause.

In the studies reviewed, most of the women were on antiepileptic drugs. Research investigating catamenial patterns in women on antiepileptic drugs is complicated and confounded by alteration of antiepileptic drug metabolism by estrogen and progesterone cyclic surges.[12,13] Thus, future research must characterize more precisely the effects of cyclic hormonal alterations on antiepileptic drug levels, metabolism, and seizure frequency. The impact of antiepileptic drugs on catamenial seizure patterns deserves further study. Relationships between catamenial patterns and different seizure types, semiologies, and syndrome classification of the type of epilepsy require closer attention in future catamenial epilepsy research.

The prevalence of catamenial epilepsy remains uncertain because of the lack of carefully designed population-based prospective studies and of a standardized definition of catamenial epilepsy as a clinical entity. Prior retrospective studies and prospective studies have found variable and contradictory prevalence estimates ranging from no correlation[3] to as high as 72%[9] of all women with epilepsy. Women with epilepsy often overestimate their catamenial seizure frequency without objective seizure count through the entire menstrual cycle.

Summary

The prevalence of catamenial epilepsy has been difficult to determine for several reasons. Menstrual cycle variability and randomness of seizure occurrence make correlation difficult.[4] Furthermore, clustering of seizures is common in males and nonmenstruating females with epilepsy[14] and is hardly unique to catamenial epilepsy. As discussed in this review, past study methodologies for determining the presence of catamenial epilepsy have not always been rigorous, and no consistent definition of catamenial epilepsy exists.

The definition proposed by Herzog, Klein, and Ransil describes three distinct patterns that may provide a sensible nomenclature for future research on catamenial epilepsy if it is validated in future population-based epidemiologic studies.[8] Without standardized inclusion criteria for catamenial epilepsy studies, the true prevalence of this disorder cannot be accurately ascertained, and treatment trials will be impossible to organize or interpret for clinical practice.

Acknowledgment

The author gratefully acknowledges the assistance of Erik St. Louis, MD, epilepitologist at Marshfield Clinic Neurosciences.

References

[1.] Ansell B, Clarke E: Epilepsy and menstruation: The role of water retention. Lancet 1956; 2: 1232-1235.

[2.] Backstrom T: Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle. Acta Neurol Scand 1976; 54: 321-347.

[3.] Bandler B, Kaufman C, Dykens J, et al: Seizures and the menstrual cycle. Am J Psychiatry 1957: 113: 704-708.

[4.] Bonuccelli U, Melis G, Paoletti A et al: Unbalanced progesterone and estradiol secretion in catamenial epilepsy. Epilepsy Res 1989; 3: 100-106.

[5.] Dickerson W: The effect of menstruation on seizure incidence. J Nervous Mental Dis 1941; 94: 160-169.

[6.] Duncan S, Read C, Brodie M: How common is catamenial epilepsy? Epilepsia 1993; 34(5): 827-830.

[7.] Healey F: Menstruation in relation to mental disorders. J Ment Sci 1928; 74: 488-492.

[8.] Herzog A, Klein P, Ransil B: Three patterns of catamenial epilepsy. Epilepsia 1997; 38(10): 1082-1088.

[9.] Laidlaw J: Catamenial epilepsy. Lancet 1956; 2: 1235-1237.

[10.] Liporace J: Women's issues in epilepsy: Menses, childbearing, and more. Postgrad Med 1997; 102(1): 123-138.

[11.] Newmark M, Kiffen-Penry J: Catamenial epilepsy: A review. Epilepsia 1980; 21: 281-300.

[12.] Rosciszewska D, Buntner B, Guz I, Zawisza L: Ovarian hormones, anticonvulsant drugs, and seizures during the menstrual cycle in women with epilepsy. J Neurol Neurosurg Psychiatry 1986; 49: 47-51.

[13.] Shavit G, Lerman P, Korczyn A et al: Phenytoin pharmacokinetics in catamenial epilepsy. Neurology 1984; 34: 959-961.

[14.] Tauboll E, Lundervold A, Gjerstad L: Temporal distribution of seizures in epilepsy. Epilepsy Res 1991; 8: 153-165.

Questions or comments about this article may be directed to: Karen Joy Weatherford, FNP, Marshfield Clinic, Neurology Department, 1000 North Oak Avenue, Marshfield, WI 54449. She is a family nurse practitioner.

Copyright [C]1999 American Association of Neuroscience Nurses 0047-2603/99/3106/00328$1.25
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Author:Weatherford, Karen Joy
Publication:Journal of Neuroscience Nursing
Date:Dec 1, 1999
Words:2868
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