Download 04Zahir.pdf

Contents : J Ayub Med Coll Abbottabad 2006 18(3) INFLUENCE OF STEROID HORMONES IN WOMEN WITH MILD CATAMENIAL EPILEPSY Zahir Hussain Masood A. Qureshi K. Zaki Hasan and Hasan Aziz Division of Neurology Department of Medicine Walter C. Mackenzie Health Sciences Centre University of Alberta Edmonton Alberta Canada T6G 2B7 Ziauddin Medical University 4/B Shahrah-e -Ghalib Block 6 Clifton Karachi-75600 Pakistan Department of Neurology Jinnah Postgraduate Medical Centre Karachi Pakistan Background: In view of considerable differences of opinion regarding the reproductive steroid hormonal pathogenesis in catamenial epilepsy hormonal analysis of estrogen and progesterone in catamenial epileptics for a precise correlation is of significant importance. Methods: Clinical neurological and physiological assessments and radioimmunoassay of plasma estradiol-17 and progesterone a day prior to the onset of menstruation were carried out in noncatamenial and mild catamenial epileptics having multiple frequency tonic-clonic (primary and secondary generalized) seizures. Results: Highly significant rise (p 0.0001) of estradiol-17 was obtained for catamenial epileptics compared to normal subjects as well as noncatamenial epileptics (p 0.02). However nonsignificant fluctuations of progesterone were found for both catamenial and noncatamenial epileptics against normal subjects as well as catamenial versus noncatamenial epileptics. Conclusions: The present report suggests that estradiol have a precise role in the mild premenstrual exacerbation of seizures. However no significant change in progesterone levels might have been due to mild exacerbation of seizures in these patients. Furthermore we suggest the importance of how we collect and categorize the data and which pathophysiologic process/ clinicobiological mechanism is involved in patients with catamenial epilepsy. Contradictory results in literature may be related to differential levels of excitation/inhibition equilibrium during various cycle phases. More precise studies including the determination of the blood levels of antiepileptic drugs however are required. Key Words: Estradiol progesterone mild catamenial epilepsy INTRODUCTION Catamenial epilepsy is considered as a menstrual cycle-related seizure disorder and is characterized by an increase in seizures during particular phases of the menstrual cycle 1 . Immediately or several days before menstruation however is considered as the most prevalent pattern2-4 . Role of estrogen and/ or progesterone in relation to catamenial epilepsy has been studied by several investigators10-12 . However there have been considerable differences of opinion regarding the hormonal pathogenesis of the catamenial exacerbation of epileptic seizures 3 5 7. Thus hormonal analysis of estrogen and progesterone in catamenial epileptics for a precise correlation is of significant importance. Although a convulsive effect of estrogen have been shown 13 one study however involving estimation of ovarian hormone levels during the menstrual cycle of patients with epilepsy6 have not confirmed the earlier suggestion by Logothetis et al.13 that high levels of estrogen are responsible for the catamenial exacerbation of seizures. Pennell et al.14 also did not find consistent correlation between average daily seizure frequency and hormonal levels in one woman with perimenstrual seizures. On the other hand the effect of intravenous progesterone infusions on epileptic discharge frequency15 indicated a significant decrease in spike frequency in few of the patients studied. These studies stress the importance of investigating the precise role of estradiol and progesterone in women with catamenial and noncatamenial epilepsy. Therefore the main objective of the present study is to test the hypothesis that estrogen and/ or progesterone play important role in the pathogenesis of catamenial epilepsy. Elucidation of this information may help to have particular social and medical measures to reduce the incidence of mild and severe forms of catamenial epilepsy. MATERIAL AND METHODS Non-catamenial epileptics (NCEp n: 236) and catamenial epileptics (CEp n: 164) having tonicclonic (primary and secondary generalized) seizures were observed mainly at the Department of Neurology (formerly Department of Neuropsychiatry) Jinnah Postgraduate Medical Centre (JPMC) Karachi during 1984 to 1988 and 1990 to 2001. Normal young women (N n: 105) served as control subjects. Body weight (Lbs.) in normal subjects non-catamenial epileptics and catamenial epileptics was in the range of 71-138 72131 and 62-125 respectively. Radioimmunoassay (RIA) determination for steroid hormones were carried out at a WHO collaborative "National 17 J Ayub Med Coll Abbottabad 2006 18(3) Research Institute of Fertility control" (NRIFC) Karachi. Detailed methods of the clinical physiological neurological and hormonal evaluations are mentioned elsewhere 3 8 . In the present report we applied the definition of catamenial epilepsy and catamenial epileptic seizures as described by Gastaut16 in the Dictionary of Epilepsy. For statistical evaluation of the present part of data arithmetic mean standard error of the mean Student's t test z test and correlation coefficient r' were performed and significance values (p) were determined. Any past history of CNS insult family history of epilepsy CNS disorders accident and also consanguinity were recorded. The patient was asked to describe pre-ictal ictal and post-ictal sensations. The cards also had information on seizure frequency duration of each attack time of seizure occurrence any aura and whether seizures affected one or both sides of the body. Specific questions were asked whether any stimuli or precipitants e.g. loss of sleep fever tiredness noise emotional disturbances photosensitivity etc. provoked a seizure. Also whether it was clonic tonic or tonic-clonic partial or complete loss of consciousness during the attack. Records were obtained for incontinence tongue biting and injury age of onset of the disorder duration of illness previous and present record of medication and efficacy of prescribed drugs (mainly carbamazepine phenytoin phenobarbitone primidone ethosuximide valproate etc). The required dosages of combined drug polypharmacy were prescribed while relying on the drug blood levels already established. Nausea vomiting headache todds paralysis and other postictal phenomena were noted and clinical tests (EEG radiological biochemical) were performed. Complete neurological examination and differential diagnosis of epileptic seizures was considered and faints (syncope) sleep dis orders hysteria other disorders resembling epilepsy like Meniere's disease hyperventilation or breathing attacks drop attacks carotid sinus disorder nervous ticks etc. were excluded. Initial data from Pakistan18 and personal experience of dealing with epileptic women for few months lead to the decision to select and follow up non-catamenial and catamenial epileptics with only tonic-clonic (primary generalized and secondary generalized) seizures 17 . Various tests of these patients were performed. The subjects having previous 4 menstrual cycles as regular (cycle length: 25-35 days) were included in the study. Duration of menstrual cycle was considered from the first day of menstrual bleeding (included) to the first day of next bleeding (excluded). One day prior to the onset of menstruation was designated as day 13 . Record of menstruation duration and basal body temperature (BBT) was also obtained to analyze the cycle length and ovulatory nature of the cycle. Samples of blood were taken and plasma separated. Samples were stored at -20 C till needed for assay. The samples required for steroid assay were obtained from extraction of plasma with equal amount of diethylether (50: 50) following the method as recommended by WHO. The detailed RIA methods and preparation of standards for estrogen and progesterone are mentioned in a previous comprehensive report 3 . RESULTS One day prior to the onset of menstruation (day 1) in normal subjects and women patients with noncatamenial and catamenial epilepsy was studied (Table I). Mean seizure occurrence (average 1 -3 seizures) on day 1 in epileptics with seizures of multiple frequency patterns was significantly higher in catamenial compared to non-catamenial epileptics (p 0.05). Age of the patients and normal subjects did not vary significantly. No significant variations in menstruation duration were found. Comparison for cycle duration showed significant variation (p 0.001 Table I) for catamenial against noncatamenial epileptics only for those patients having cycle duration less than 28 days. Estradiol values (mean S.E.M) for normal subjects and women with noncatamenial and catamenial epilepsy are given in Table I. Highly significant rise (p 0.0001) was obtained for catamenial epileptics compared to normal subjects as well as noncatamenial epileptics (p 0.02). However noncatamenial epileptics compared to normal subjects did not show significant variations. Correlation coefficient r' for seizures against plasma estradiol showed nonsignificant correlation (p 0.05) for both group of patients. Mean S.E.M values of progesterone for normal subjects and patients with noncatamenial and catamenial epilepsy are given in Table I. Analysis indicated nonsignificant fluctuations for both catamenial and noncatamenial epileptics against normal subjects as well as catamenial versus noncatamenial epileptics. The values of r' showed no definite relationship found for seizure occurrence against progesterone levels. 18 J Ayub Med Coll Abbottabad 2006 18(3) Table-1: Steroid hormones and reproductive profile in patients with catamenial/ noncatamenial epilepsy. Parameters Normal subjects (N) (n: 105) 4.78 0.05 28.63 0.12 222.48 9.42 (76) 14.29 0.85 (76) Noncatamenial epileptics (NCEp) (n:236) 4.86 0.04 28.60 0.07 242.95 5.84 (143) 15.49 0.55 (143) Catamenial epileptics (CEp) (n:164) 4.95 0.06 28.50 0.10 264.89 8.53 (92) 13.69 0.80 (92) Significance (p) NCEp vs N 0.05 CEp vs NCEp 0.05 CEp vs N 0.05 Menstruation duration (days) Cycle duration (days) Estradiol-17 (pmol/l) Progesterone (nmol/l) 0.05 0.05 0.001 0.02 0.05 0.0001 0.05 0.05 0.05 Figures in parentheses denote total number of samples the data of age menstruation duration and cycle duration is of all subjects. pathophysiological processes/ mechanisms in these DISCUSSION patients might have been different. This background may explain the difference in the positions taken by In the present study the pattern of estradiol and two eminent researchers where Laidlaw20 was more progesterone concentration is similar to that in in favor of progesterone hypothesis and Logothetis 13 normal subjects19 and those with epilepsy7 . Majority was more inclined to implicate estrogen. of the women studied by Backstrom5 also shows a The present study suggests that some similar pattern. The results of the subjects with specific alteration in neural and hypothalamo multiple seizure frequency pattern in the present hypophyseal-ovarian (H-H-O) complex may be the investigation though resemble to other reports in stimuli that result in changing hormone levels 3 17. respect to some aspects of the patients' categorization This view may also explain the significant variations and neurological and hormonal evaluations6 7 8 it found in estradiol for normals and non-catamenial was restricted to the study of one day prior to the start and catamenial epileptics. The results of estrogen of menstruation that helped comparing precise activation hypothesis 13 in this respect are in hormonal variations in catamenial and noncatamenial agreement with animal experimentation21 . On the epileptics. basis of our previous investigations3 8 and present Significant variation of seizure occurrence work we suggest that it is probably not the variation (p 0.05) with corresponding estradiol variations (p of estrogen or progesterone or any other particular 0.02) shows that a relationship exists between hormone/ factor causing all sub-types of catamenial estradiol levels and seizures in catamenial epileptics epilepsy/ epilepsy during menstrual cycle. Rather it is and estradiol have a precise role in the premenstrual how we gather and categorize the data and which exacerbation of seizures. Furthermore the pathophysiologic process/ clinicobiological comparison with normal subjects showing highly mechanism is involved in certain group of patients significant change in estradiol only in catamenial with noncatamenial/ catamenial epilepsy. Further epileptics confirming our previous reports2 8 clarified work is obviously required to interpret the that possibly the prescribed treatment did not alter the controversial views in literature. plasma estradiol levels. No significant change in progesterone levels CONCLUSIONS seems to be due to a different dispersion pattern of seizures in these patients compared to our another Contradictory results for the role of gonadosteroids in group of patients with severe catamenial epilepsy8 . literature may be related to differential levels of Instead of seizures occurring mainly or exclusively excitation/inhibition equilibrium during various cycle during premenstruation the present group of patients phases22 . Although previous investigations which had seizures also during other cycle phases though included determination of blood levels of the quite less in number than during premenstruation. In antiepileptic drugs did not find any significant view of this the term mild catamenial or semivariations in levels of antiepileptic drugs more catamenial may be used for those patients who have a precise studies including the determination of the mild exacerbation. This may suggest that the blood levels of antiepileptic drugs are required. This 19 J Ayub Med Coll Abbottabad 2006 18(3) may help understanding the precise role of reproductive steroid hormones in catamenial epilepsy. 10. 11. Herzog AG frye CA. Seizure exacerbation associated wiyh inhibition of progesterone metabolism. Ann Neurol 2003 53:390-1. Morrell MJ Flynn KL Done S Flaster E Kalayjian L Pack AM. Sexual dysfunction sex steroid hormone abnormalities and depression in women with epilepsy treated with antiepileptic drugs. Epilepsy & Behavior 2005 6: 360-65. Logothetis J Harner R Morrell F Torres F. The role of estrogens in catamenial exacerbation of epilepsy. Neurology 1959 9: 352-60. Pennell PB Selliah RN Henry TR. Relationships between serum sex steroid hormone levels antiepileptic drug levels and seizure frequency in catamenial epilepsy. Epilepsia 1999 40: 238. Abstract Backstrom T Zetterlund B Blum S Romano M. Effects of intravenous progesterone infusions on the epileptic discharge frequency in women with epilepsy. Acta Neurol Scand 1984 69: 240-48. Gastaut H. Dictionary of epilepsy. Part 1: Definitions. Geneva: WHO 1973. Azeemi ZH Qureshi MA Hasan KZ Aziz H. (1987) Effect of anticonvulsants on seizure occurrence in women with epilepsy. Annals of JPMC 1987 4:13-18. Aziz H Ali SM Francis P Hasan KZ. Demography and classification of epilepsy (on 2357 patients of epilepsy). Annals of JPMC 1986 3: 11-15. Liu SF Wang ZX Yuan YE Bing SM zhang BZ Wu JZ et al. Hormone changes during the menstrual cycle of Chinese women. J Repro Fert 1986 76:43-52. Laidlaw J. Catamenial epilepsy. Lancet 1956 2: 1235-37. Woolley CS. Estradiol facilitates kainic acid-induced but not flurothyl-induced behavioral seizure activity in adult female rats. Epilepsia 2000 41: 510-15. Azeemi ZH Qureshi MA Hasan KZ Aziz H. Fluctuations of plasma gonadotropins in medicated epileptics and pathophysiological interpretation of catamenial seizures. Pak Med J 1990 13:12-14. REFERENCES 1. 2. Reddy DS. Role of neurosteroids in catamenial epilepsy. Epilepsy Res 2004 62: 99-118. Qureshi MA Azeemi ZH Aziz H Hasan KZ. Changes in estrogen and progesterone seizure occurrence and effect of anticonvulsant medication in catamenial epileptics. Fed Amer Soc Exp Biol J 1988 2: 4500. Abstract Hussain Z. Clinical electroencephalographic and hormonal study in menstruation related seizures. Ph.D. thesis. Karachi: University of Karachi 1993. 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: 431-4. Backstrom T. Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle. Acta Neurol Scandinav 1976 54: 321-47. Rosciszewska D. Analysis of seizure dispersion during menstrual cycle in women with epilepsy. Monog Neurol Sci 1980 5: 280-284. Jacono JJ Robertsson JMD. The effects of estrogens progesterone and ionized calcium on seizures during the menstrual cycle of epileptic women. Epilepsia 1987 28: 571-7. Hussain Z Qureshi MA Hasan KZ Aziz H Zafar F Siddiqui U. Changes in estrogen and progesterone seizure occurrence and effect of anticonvulsant medication in catamenial epileptics. Med Biol J 1994 2: 10-29. Reddy DS Rogawski MA. Enhanced anticonvulsant activity of neuroactive steroids in a rat model of catamenial epilepsy. Epilepsia 2001 42: 337-44. 12. 13. 3. 4. 14. 5. 6. 7. 15. 16. 17. 18. 19. 20. 21. 8. 9. Addresses For Correspondence: Dr. Zahir Hussain 201-10533 83 Ave Edmonton Alberta Canada T6E 2E1. Telephone: 780-989-1390 Home Address in Pakistan: 1. Dr Zahir Hussain S/O Chaudhary Haji Mohammad Akbar (Late) Village & Post Office: Bhadana Tehsil: Gujar Khan District: Rawalpindi Pakistan 2. Dr. Zahir Hussain R-113 Block-6 Gulshan-e-Iqbal Karachi-75300 Pakistan E-mail: z a hus@yahoo.ca 20

INFO HASH : 260e920decbddd6a85665354c0ddbcb8c8662471

Download now

File Size: 27.9 kb