Introduction: Burden of Epilepsy

Epilepsy is one of the most common disorders affecting the neurological (nervous) system and one of the most complex. It is best regarded as a series of disorders, called epilepsy syndromes. Epilepsy is characterised by recurrent, unprovoked seizures, which are due to excessive, uncontrolled electrical activity in the brain. It is thought to affect 40-70 per 100,000 persons per year in developed countries, and even more people in less developed countries. Prevalence is approximately 4-10 per 1000. Over seventy per cent of patients will enter remission (ie disease activity is controlled and stopped) on treatment with the first drug. There is a significantly higher risk of SUDEP (sudden unexplained death) in people with epilepsy than in the general population. Seizures can harm the brain, and should be controlled early in the course of the condition. If you suffer from epilepsy, all seizures should be taken seriously, as anoxia (complete absence of oxygen), injury, more seizures, and metabolic complications may arise.

The Burden of Epilepsy

If you are affected by epilepsy or know someone who suffers from epilepsy, you may experience problems such as; the risk of seizures occuring and sustaining injuries from these seizures, restrictions on driving and drinking alcohol, and being unable to enjoy good sleep. You may also find it harder to find a suitable job. Some jobs may prefer to employ people who do not suffer from epilepsy, because you may be put at risk if you experience an epileptic seizure at work – for example; you will not be able to be employed in any job that involves operating any heavy machinery. Organisations such as the Epilepsy Association and also medical professionals are trying to make these restrictions as fair as possible.

Both established and newly introduced medications to treat epilepsy may produce side effects. Some are quite specific to each drug. Some of these side effects affect the reproductive system, including; affecting hormone levels, and polycystic ovarian syndrome (PCOS) (comprising of lack of regular ovulation, excessive hair growth (hirsutism), insulin resistance and increased weight). These effects may occur in women who are taking valproate therapy. Enzyme inducing drugs, (phenytoin, carbamazepine and barbiturates) have been linked to affecting Vitamin D levels, resulting in bone disorders and softening of the bones (osteomalacia). In males, sperm motility and viscosity are claimed to be reduced by conventional antiepileptic drugs. As much as half of the people who are treated with epilepsy are women. Many women are of child-bearing age. In these cases, the greatest concern to you or your partner with epilepsy would be whether your child will inherit epilepsy. The inheritance of epilepsy is complex, but there is certainly a strong link to genetic factors. It is influenced by the type of epilepsy, and the presence of the disorder in one or both parents, and the frequency with which it is present in near relatives. Counselling is available and may be helpful to obtain an estimate of the risk of your child inheriting epilepsy from you and/or your partner.

Drug related questions to the Burden of Epilepsy: The Role of Pregnancy Registers

It is difficult to accurately answer the question of epilepsy drug related malformations when women are taking medications during pregnancy. We cannot experiment with drugs in pregnancy. When we review data from pregnant women who have been affected by epilepsy, data on malformations suggests that if you take more than one drug during pregnancy, there is an increased risk to the unborn child. If you are on treatment for epilepsy, there have been some women who experience more side effects than others during pregnancy. However, seizures themselves can be harmful to the baby. All studies on antiepileptic medications during pregnancy have different designs and generally small numbers of women studied. None of the new antiepileptics have been studied in a systemic, stepwise manner, for their effects on babies. No specific drug has yet been linked to a single defect. In terms of physical malformations and deformities, it has been suspected since 1979 that Valproate was significantly more dangerous than other drugs. It has been confirmed that high dose valproate is hazardous. However, studies examining the effects that will occur with ongoing, longer term use of this drug are lacking.

Pregnancy Registers

Pregnancy Registers have been established to help collect information for further research, to provide you with more information on antiepileptic treatment effects during pregnancy. After approval is gained from ethical committees and written consent is given by the patients’ involved, four telephone interviews and access to patients’ medical records are obtained. This data was studied through a process of observing and analysing what had happened during pregnancy. Pregnancy Registers are a list of records of women who are pregnant, which can help to gather data on the outcome of pregnancies in women with epilepsy. These registers aim to record and assess the number of unwanted outcomes affecting the baby, resulting from antiepileptic drugs taken during pregnancy.They also aim to determine if certain drugs, or combinations, are associated with a higher incidence of side effects. The importance of factors such as the pregnant woman experiencing seizures during pregnancy, epilepsy syndromes, the parent’s genetic background, and environmental factors are examined.

The efficacy of antiepileptic drugs on seizure protection in pregnancy is also evaluated. This is based on women reporting their experiences / side effects or a need for increased drug levels to control seizures. Women are recruited into the Australian Pregnancy Register by letters and pamphlets sent out to neurologists (specialized doctors who diagnose and treat disorders of the nervous system), obstetricians, specialists, untrained people within the general population, and maternity hospitals. Support by the Epilepsy Society of Australia is very important. Since 1999, Victoria, NSW and Queensland have had quite high levels of enrolments, followed by WA, SA, ACT and Tasmania. Around 5,000 patients are required to accurately assess the effects of exposure to each type of antiepileptic drug. Therefore, links with international Register, EURAP, have been established.

Trends & Results of The Burden of Epilepsy

Results after 75 months of follow up, from the Australian Pregnancy Registry, indicate that there were 803 live normal births, including 14 sets of twins, and two babies from two twin sets. There were 33 live births with defects, with 12 defects detected at twelve months after delivery. There were 45 miscarriages, the majority occurring spontaneously. Thus the outcome of a normal baby can be anticipated in over 90 per cent of mothers with epilepsy. If miscarriages were regarded as a separate category, 95 per cent the babies appear be free of physical defects. These figures are quite good, giving a favourable and positive outlook for mothers affected by epilepsy, of having a child who is unaffected by epilepsy. The other major, specific finding reported was an unacceptably high level of malformation risk associated with high doses of valproate at doses above 1100 mg per day. Doses below that level were not linked to a significant difference between drugs. However, if a pregnant woman was on valproate, there was an increased rate of malformations compared to those who did not receive the drug.

The Register also addressed the control of seizures. Good seizure control is important to obtain during pregnancy, as a seizure occuring during pregnancy can affect the baby, depriving them of oxygen and resulting in foetal losses. Although lamotrigine may be safer for the baby than valproate, an analysis was made on how drugs used alone (ie valproate, lamotrigine and carbamazepine) affected seizure control. The endpoint was based on reported seizure activity, and alterations in the levels of drugs required to acheive control. For all types of seizures, valproate was significantly more effective than lamotrigine. Thus although it is associated with less side effects, lamotrigine is not as effective as valproate. If you are taking antiepileptic drugs during pregnancy, there has to be a balance between the risks of drug side effects, compared to the level of control you are offered with the drug.

Overview of The Burden of Epilepsy: The Role of Pregnancy Registers

If you are affected by epilepsy, education on the effects of epilepsy on your pregnancy should be provided by your local doctor or appropriate health professional. If you have any questions on epilepsy and pregnancy, you should seek the advice of your local doctor. Often, you will be given information on a range of issues, such as explaination that a balance must be maintained between risks of seizures to both the mother and baby, and safety of your child. High dose valproate poses an unacceptable risk to pregnancies, but valproate is more effective than lamotrigine. Older drugs, phenytoin and carbamazepine as well as lamotrigine have a comparable incidence of malformation rates, lower than valproate. Valproate may play a role in helping control epilepsy in some patients, despite it’s increased risk of side effects. Changing medication once pregnancy had occurred should be done with caution, with a specialist opinion. A part of your doctor’s role includes helping you plan your pregnancy, and discuss options early, to establish optimal control before pregnancy occurs. You should not hesitate to seek your local doctor’s advice.

Recommendations such as pre-conception folic acid, 5mg twice daily, have been established, based on studies in pregnant women, without epilepsy. In the Australian Pregnancy Register, more and more women are being enrolled, demonstrating the understanding of the importance of data provided. Prescribing patterns are changing, with a fall in doses and numbers of valproate related prescriptions. Doses of lamotrigine have risen, but this has resulted in an increase in reported malformations. A causal relationship between the dose of lamotrigine and risk of malformations in unborn babies is possible and has been reported. The impression of lamotrigine being less effective than valproate has been confirmed in limited studies. Research continues to be performed in the area of untreated patients and effects of antiepileptic drugs and epilepsy on cognition (knowledge and processing of data) are under investigation.

References

  1. Tomson T, Perucca E and Battion D. Navigating toward Fetal and Maternal Health. Epilepsia 2004; 45(10):1171-75
  2. Sabers A, Buchholt J, Uldall P, and Hansen EL. Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Research 2001; 47:151-154
  3. Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E, Sabers A, and Vajda F . Drug Registries. EURAP: An international Registry of Antiepileptic Drugs and Pregnancy Epilepsia 2004. ;45:1463
  4. Vajda FJ, Lander CM, Hitchcock A, Graham J, O’Brien TJ and Eadie MJ. Foetal malformations and seizure control: 52 months data of the Australian Pregnancy Registry European J. Neurology 2006;13;645-654
  5. Holmes LB, Wyszynski MD, Leberman E .The AED (Antiepileptic Drug) Pregnancy Registry. Arch Neurol 2004;(61):6723-678
  6. Morrow JJ and Craig JJ. Antiepileptic drugs in pregnancy:current safety and other issues Expert Opin. Pharmacother.2003;4(4):445-456
  7. Vajda FJE, O’Brien TJ, Graham J, Hitchcock A, Lander CM, Eadie MJ. The pregnancies in women with epilepsy. J.Royal College of Physicians of Edinburgh. 2006;36:201-207
  8. Vajda FJE, O’Brien TJ, Hitchcock A, Graham J, Lander CM, Eadie MJ. Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of antiepileptic drugs in pregnancy. J. Clin. Neuroscience 2004;11(8):854-858
  9. Vajda FJ, Lander CM, Hitchcock A, Graham J, O’Brien TJ and Edaie MJ. Update and trends from the Australian Pregnancy register: 75 months data. Annual Scientific Meeting, Epilepsy Society of Australia, Melbourne 4-9.October 2006-10-16
  10. Craig J, Perucca E, Sabers A, Tomson T, Vajda F, Battino D, Bonizzoni E, and Lindhout D. Seizure control and treatment in pregnancy: Observations from the EURAP Epilepsy Pregnancy Registry Neurology 2006; 66(3):354-360
  11. Meador KJ, Baker GA, Finnell RH et al. In utero antiepileptic drug exposure. Neurology 2006;67:407-41
  12. Vajda F, OBrien T, Graham J. Hitchcock, Lander C and Eadie M. The value of an untreated internal control group in the Pregnancy-Antiepileptic Drug Register. Submitted for publication. J.Clinical Neuroscience, September 2006, revised October 2006

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