Special Medical Reports

New Guidelines Offer Recommendations for Women with Epilepsy

VERNA L. ROSE

New guidelines for women with epilepsy have been issued by the American Academy of Neurology (AAN). A summary statement of the practice parameter was published in the October 1998 issue of Neurology. It is accompanied by a review of the literature referable to the management of women with epilepsy. The recommendations in the practice parameter are intended to help women with epilepsy make decisions about contraception, pregnancy and breast feeding while effectively managing the disease.

Management Issues for Women with Epilepsy During reproductive years What is the best antiepileptic drug regimen during the reproductive years? What is the best contraceptive plan? What is the role of folic acid supplementation during the reproductive years? How should seizures related to cyclic hormonal fluctuation be managed? What are the appropriate topics for prepregnancy counseling? During and after pregnancy How should antiepileptic drug levels be monitored and adjusted during pregnancy? What is the role of vitamin K use during pregnancy? What recommendations can be made regarding breast feeding? How should antiepileptic drug dosages be altered in the postpartum period? Reprinted with permission from Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: Management issues for women with epilepsy (summary statement). Neurology 1998;51:944-8.

The development of this parameter was undertaken by members of the AAN Quality Standards Subcommittee in conjunction with the American Epilepsy Society, the Epilepsy Foundation and the Child Neurology Society (CNS). Parameter drafts were reviewed by selected experts in epilepsy and of the American College of Obstetrics and Gynecology, the American Academy of Pediatrics and the CNS.

According to the guidelines, there are potentially over 1 million women with epilepsy of childbearing age in the United States. The authors of the guidelines emphasize that the issues for these women are complex and multifaceted, and many women with epilepsy and their health care professionals need more information about these issues. The issues covered in the guidelines include the risk of birth defects in children born to women taking antiepileptic drugs, contraception, seizures and hormonal fluctuations, management during pregnancy, counseling, breast feeding and adjustment of medication after pregnancy (see table).

The following are the guidelines that have been proposed by the AAN:

• Because antiepileptic medications can increase the risk of birth defects, using only one antiepileptic drug should be the goal in women of childbearing age. The drug selected for use should be the most appropriate for the woman's seizure type. Drug therapy should be optimized before conception, if possible. If drug withdrawal is planned, withdrawal should be completed at least six months before conception. A change in medications should not be undertaken solely for the purpose of reducing teratogenic risk.
• As is recommended for the general female population, all women with epilepsy should take folic acid supplementation of no less than 0.4 mg per day.
• Because some antiepileptic drugs can decrease the effectiveness of oral contraceptives, women with epilepsy should be counseled concerning the preferred method of birth control.
• During pregnancy, women with epilepsy, especially those treated with carbamazepine, divalproex sodium or valproic acid, should be offered prenatal testing with alpha-fetoprotein levels at 14 to 16 weeks of gestation, level II ultrasound at 16 to 20 weeks of gestation, and, if needed, amniocentesis for amniotic fluid alpha-fetoprotein and acetylcholinesterase levels.
• Breast feeding can be recommended as an option for infants of women with epilepsy. According to the AAN, there are no absolute contraindications to breast feeding in these infants. However, these infants should be closely monitored.

The practice parameter also lists practice options that include counseling for the possibility of seizure frequency changes during pregnancy, importance of medication compliance, the need for regular follow-up during pregnancy and inheritance risks of seizures. Additional information for patients may be obtained from the Epilepsy Foundation at 800-EFA-1000. The Web site is http://www.efa.org.

The report calls for more research in several areas. These include well-designed studies of pregnancy outcomes for women with epilepsy, especially in women taking the new antiepileptic drugs; studies on the efficacy of hormonal contraception in women with epilepsy; studies of issues concerning seizure frequency changes through the stages of reproductive life; and the promotion of pregnancy registries to monitor the teratogenesis of antiepileptic drugs. The AAN also recommends physician education regarding management issues for women with epilepsy at all levels of training and practice.

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CDC Calls for Tuberculosis Screening and Treatment for All Patients with HIV Infection

VERNA L. ROSE

New guidelines from the Centers for Disease Control and Prevention (CDC) outline the proper evaluation and treatment of tuberculosis in individuals infected with human immunodeficiency virus (HIV). These guidelines update previous CDC recommendations for the diagnosis, treatment and prevention of tuberculosis in adults and children infected with HIV. The new guidelines were published in the October 30, 1998, issue of the recommendations and reports series of Morbidity and Mortality Weekly Report. The CDC staff member who prepared this report is M. Elsa Villarino, M.D., M.P.H., Division of TB Elimination, National Center for HIV, STD and TB Prevention.

The report emphasizes that all HIV-infected persons should be screened for tuberculosis and, if they are found to be infected with tuberculosis, they should be treated to prevent the development of active tuberculosis disease. Early diagnosis and effective treatment of tuberculosis in persons with HIV infection are critical for curing tuberculosis, minimizing the negative effects of tuberculosis on the course of HIV disease and eliminating the spread of Mycobacterium tuberculosis. All patients suspected of having tuberculosis should undergo a thorough medical evaluation, including HIV counseling and testing, unless the person has documentation of HIV testing within the past six months. The report notes that because HIV infection so severely weakens the immune system, persons infected with both HIV and tuberculosis have a 100 times greater risk of developing active tuberculosis disease and becoming infectious to others, compared with persons who have tuberculosis but who are not infected with HIV.

According to the guidelines, one main consideration in persons coinfected with tuberculosis and HIV is to avoid the use of rifampin in combination with protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rifampin can seriously decrease the effectiveness of these therapies. Two treatment options currently recommended for these patients are (1) a rifabutin-based regimen or (2) an alternative non-rifamycin regimen that includes streptomycin. Rifabutin provides the first alternative treatment to rifampin. Previously, patients had to stop taking their HIV medication until tuberculosis therapy could be completed.

Because of potential side effects and concerns about drug resistance, health care professionals should provide directly observed therapy (DOT) to HIV-infected individuals and carefully monitor them for adverse effects and progress. Other strategies to promote adherence to drug regimens should also be implemented.

The following are the treatment options for patients with HIV infection and drug-susceptible pulmonary tuberculosis that have been excerpted from the document. The letters within parentheses following the recommendation designate the strength of the recommendation: A=strong, should always be offered; B=moderate, should usually be offered; C=optional; D=should generally not be offered; and E=should never be offered. The roman numerals within the parentheses indicate the quality of evidence supporting the recommendation: I=at least one randomized trial with clinical end points; II=clinical trials with laboratory end points only or conducted only in populations not infected with HIV; III=expert opinion.

• DOT and other strategies that promote adherence to therapy should be used for all patients with HIV-related tuberculosis. (A-II)
• For patients who are receiving therapy with protease inhibitors or NNRTIs, the initial phase of a six-month tuberculosis regimen consists of isoniazid, rifabutin pyrazinamide and ethambutol. These drugs are administered (1) daily for eight weeks or (2) daily for at least the first two weeks, followed by twice-a-week dosing for six weeks, to complete the two-month induction phase. The second phase of treatment consists of isoniazid and rifabutin administered daily or twice a week for four months. (A-II)
• For patients in whom the use of rifamycins is limited or contraindicated for any reason (e.g., intolerance to rifamycins, patient/clinician decision not to combine antiretroviral therapy with rifabutin), the initial phase of a nine-month tuberculosis regimen consists of isoniazid, streptomycin, pyrazinamide and ethambutol administered either (1) daily for eight weeks or (2) daily for at least the first two weeks, followed by twice-a-week dosing for six weeks, to complete the two-month induction phase. The second phase of treatment consists of isoniazid, streptomycin and pyrazinamide administered two to three times a week for seven months. (Every effort should be made to continue administering streptomycin for the total duration of treatment or for at least four months after culture conversion. Some experts suggest that in situations in which streptomycin is not included in the regimen for all of the recommended nine months, ethambutol should be added to the regimen to replace streptomycin, and the duration of treatment should be prolonged from nine months to 12 months. Alternatives to streptomycin are the injectable drugs amikacin, kanamycin and capreomycin.) (B-II)
• For patients who are not candidates for antiretroviral therapy, or for those patients for whom a decision is made not to combine the initiation of antiretroviral therapy with tuberculosis therapy, the preferred option continues to be a six-month regimen that consists of isoniazid, rifampin, pyrazinamide and ethambutol (or streptomycin). These drugs are administered either (1) daily for eight weeks or (2) daily for at least the first two weeks, followed by two to three times per week dosing for six weeks, to complete the two-month induction phase. The second phase of treatment consists of isoniazid and rifampin administered daily or two to three times a week for four months. Isoniazid, rifampin, pyrazinamide and ethambutol (or streptomycin) also can be administered three times a week for six months. (A-I)
• Tuberculosis regimens consisting of isoniazid, ethambutol and pyrazinamide (i.e., three-drug regimens that do not contain a rifamycin, an aminoglycoside [e.g., streptomycin, amikacin, kanamycin] or capreomycin) should generally not be used for the treatment of HIV-infected patients with tuberculosis; if these regimens are used for the treatment of tuberculosis, the minimum duration of therapy should be 18 months (or 12 months after documented culture conversion). (D-II)
• Pyridoxine (vitamin B₆), 25 to 50 mg daily or 50 to 100 mg twice weekly, should be administered to all HIV-infected patients who are undergoing tuberculosis treatment with isoniazid, to reduce the occurrence of isoniazid-induced side effects in the central and peripheral nervous system. (A-II)
• Because the CDC's most recent recommendations for the use of antiretroviral therapy strongly advise against interruptions of therapy (to minimize the emergence of drug-resistant HIV strains, if any antiretroviral medication must be temporarily discontinued for any reason, clinicians and patients should be aware of the theoretical advantage of stopping all antiretroviral agents simultaneously, rather than continuing the administration of one or two of these agents alone), and because alternative tuberculosis treatments that do not contain rifampin are available, previous antituberculosis therapy options that involved stopping protease inhibitor therapy to allow the use of rifampin are no longer recommended. (E-II)

The report also covers the following topics: management strategies; appropriate doses of medication; duration of tuberculosis treatment; the medical evaluation while receiving treatment for both tuberculosis and HIV infection; the treatment of tuberculosis in special situations, such as pregnancy; and tuberculosis preventive therapy regimens.

Copies of the complete recommendations can be obtained by calling the Division of TB Elimination at 404-639-8063. Copies can also be downloaded from the Division's Web site at http://www.cdc.gov/nchstp/tb.

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ACOG Releases a Statement on Identification and Treatment of Adolescent Victims of Sexual Assault

VERNA L. ROSE

In an educational bulletin published in the October 1998 issue of Obstetrics and Gynecology, the American College of Obstetricians and Gynecologists (ACOG) discusses the management of adolescent victims of sexual assault (ACOG Educational Bulletin No. 252). The report covers definitions, prevalence, adolescent perceptions of violence, identification of the adolescent sexual assault victim, and intervention and prevention.

The National Institute of Justice reports that, each year, 1 million women in the United States become new victims of rape. ACOG points out that many of these victims are adolescent females and children. One study mentioned in the report provided evidence that 74 percent of women who had sex before the age of 14 years and 60 percent of women who had sex before the age of 15 years had sex involuntarily at some time earlier in their lives. ACOG believes that these data suggest routine screening is warranted for adolescent victims of sexual assault so that they may receive appropriate counseling.

ACOG recommends that physicians who evaluate victims of acute sexual assault should provide counseling as well as medical treatment, talk to the victim about her rights, direct her to obtain legal assistance and discuss preventive strategies for future problems with victimization. However, ACOG recognizes that physicians may be faced with the challenging responsibility of identifying adolescent victims of sexual assault and providing effective interventional and preventive counseling. It is important for physicians to recognize the behavioral symptoms that may suggest a history of sexual assault. In the report, ACOG lists the following behavioral and psychologic symptoms that may help identify an adolescent who has been sexually assaulted in the past: teenage pregnancy, poor contraceptive use, substance abuse, risky health behaviors associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome, prostitution, multiple sexual partners, sexual dysfunction, problems with interpersonal and sexual relations, poor self-esteem, depression, somatization, eating disorders/obesity, insomnia and nightmares, suicide attempts, psychiatric admissions, post-traumatic stress disorder, anxiety and school failure.

The following physical health problems that may suggest a history of sexual assault are listed in the ACOG report:

• Chronic abdominal pain
• Gastrointestinal tract symptoms (e.g., irritable bowel syndrome)
• Chronic pelvic pain
• Vulvodynia and dyspareunia
• Breast pain
• Gynecologic infections
• Sexual transmissible infections
• Chronic headache
• Musculoskeletal complaints
• Multiple physical complaints

The ACOG document also discusses the physician's responsibility for reporting child abuse to child protective services and various effective counseling techniques. Suggestions for prevention messages for adolescents are also included.

The address for ACOG is 409 12th St., S.W., P.O. Box 96920, Washington, D.C. 20090-6920.

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