EPILEPSY IN PREGNANCY

DEFINITION OF EPILEPSY Epilepsy is recurring spontaneous seizures due to sudden excessive and disordered electrical discharge from the neurones of the Cerebral cortex.A chronic neurologic disorder manifesting by repeated epileptic seizures (attacks or fits) which result from paroxysmal uncontrolled discharges of neurons within the central nervous system

INCIDENCE OF EPILEPSY Approximately 50 million women currently live with epilepsy worldwide. The estimated proportion of the general population with active epilepsy. 7% of epileptic women become pregnant. Epilepsy affects about 0.5-1% of pregnant women.

Pathogenesis The 19th century neurologist Hughlings Jackson suggested “a sudden excessive disorderly discharge of cerebral neurons“ as the causation of epileptic seizures. Recent studies of focal epilepsy suggests a central role for the excitatory neurotransmiter glutamate (increased in epilepsy) and inhibitory gamma amino butyric acid (GABA) (decreased)

A seizure is the clinical manifestation of epilepsy. This occurs basically due to excessive firing of the neurons and fast spread of these impulses over the brain. Thus there are two phenomenons in the pathophysiology of a seizure:- 1. Hyper-excitability of a neuron 2. Hyper synchronization Hyper synchronization means that a hyper-excitable neuron leads to excessive excitability of a large group of surrounding neurons.

Transmission There are two types of transmission of impulses - excitatory and inhibitory. Excitatory transmission involves Glutamate that is the principal excitatory neurotransmitter in the brain. GABA or Gamma amino butyric acid is the principal inhibitory neurotransmitter in the brain. There are two groups of glutamate receptors - Ionotropic (NMDA receptors) that modulate calcium and sodium channels and are responsible for fast synaptic transmission and Metabotropic (non NMDA receptors) that are for slow synaptic transmission. GABA is mediated via Chloride and Potassium channels

RISK FACTORS RELATED TO EPILEPSY About 1% of the general population develops epilepsy The risk is higher in people with certain medical conditions: 1.Traumatic Brain Injury 2.Stroke 3.Alzheimer’s disease 4.Autism 5.Brain Tumors or blood vessel abnormalities

CAUSES OF EPILEPSY IN PREGNANCY - In about 70% of people with epilepsy, the cause is not known. - In the remaining 30%, the most common causes are: 1.Head trauma 2.Infection of brain 3.Brain tumor and stroke 4.Heridty

SIGNS THAT INDICATE EPILEPSY  Periods of blackout or confused memory  Occasional “fainting spells”  Episodes of blank staring in children  Sudden falls for no apparent reason  Episodes of blinking or chewing at inappropriate times

THE EFFECT OF PREGNANCY ON EPILEPSY THE EFFECT OF PREGNANCY ON EPILEPSY IS UNCERTAIN Frequency of convulsions is unchanged in majority (50%). The frequency of convulsions is unchanged in majority (50%), increased in 45% and decreased in about 5% of women. Serum concentration of anti convulsant falls in pregnancy. All anti convulsants interfere with folic acid metabolism. Folic acid deficiency has been associated with neural tube defects and other congenital malformations.

EFFECTS OF EPILEPSY ON PREGnANACY Incidence of fetal malformations:-  IUGR  Oligohydramnios  Preeclampsia  Still births  Birth defects are increased by two folds. - Pattern of abnormalities is related to the type of anticonvulsant drug. (valproate 5.9%, carbamazepine2.3% and Lamotrigine2.1%)

THE MALFORMATION INCLUDES  Cleft lip and/or palate  Mental retardation  Cardiac abnormalities  Limb defects  Hypoplasia of the terminal phalanges  Neural tube defects (because of deficiency of sodium valproate)  Neonatal hemorrhage is related to anticonvulsant induced reduction of coagulation factors (vitamin k dependent)  Risk of developing epilepsy to the offspring of an epileptic mother is 10%.

Neural tube defect.. Myelomeningocele Anencephaly

Cleft lip and palate..

PRECONCEPTION COUNCELLING It includes:  To initiate monotherapy (if possible) replacing polytherapy  To administer folic acid 4mg daily  Importance of prenatal diagnosis is to be discussed.

MANAGEMENT OF EPILEPSY IN PREGNANCY

The dose of choosen drug should be kept as low as possible. Valproate and phenytoin are found to be most teratogenic. The commonly used drugs are: 1.Carbamazepine mg daily in divided doses, 2.Phenytoin mg daily in two divided doses, 3.Lamotrigine mg /day is given (not an enzyme inducer) Newer drugs used with safety are: 1.Topiramate( mg/day) 2.Levetiracetam 1-3 gm/day (not enzyme inducer)

Serum levels may be measured in patients with frequent seizures to assess therapeutic levels and compliance. Fits are controlled by IV phenytoin with a slow loading dose of 15-20mg/kg. it is highly effective, has a long duration of action and side effects are less. Otherwise, Benzodiazepine 10-20mg slow IV may be given. Folic acid 4mg daily is to be started before pregnancy and to be continued throughout.

Prenatal diagnosis by ultrasonography including fetal echocardiography should be done. There is free level of most of the anticonvulsants in the pregnancy. The reasons are: Delayed gastric emptying  Reduced absorption  Increased protein binding  Nausea  Vomiting  Increase in plasma volume  Increased hepatic metabolism

I-PRECONCEPTIONAL CARE A-Re-assessment: may show that the patient does not have epilepsy or may reveal a treatable cause before pregnancy (e.g. blood vessel abnormality in the brain). B-Counseling: explain to the patient that: There is a chance of 90% of having normal child. Increased chance of having epileptic child (2-5%). Increased pregnancy complications. Increased unfortunate outcome if seizures arises during pregnancy. Increased risk of congenital malformations.

II- ANTENATAL CARE A-Investigations: Metabolic: serum glucose, urea, electrolytes, Ca & Mg EEG MRI/CT scan of the head. B-Drugs: Monotherapy at the lowest effective dose should be employed. If large daily doses are needed, use frequent smaller doses or extended-release formula to avoid high peak levels. Monitoring of serum AEDs level is mandatory. Usually, women don't suspect they are pregnant until their fourth to sixth week of pregnancy. By that time, if there are any harmful effects from their AEDs, most of these effects would have already occurred.

C-Selenium supplementation: in a dose of 200 µ/day may be important to minimize the free radical mediated damage. D-Folic acid supplements. E-Morning sickness: If hyperemesis gravidarum, consider giving alternative route if vomiting is severe or prolonged. F-Antenatal diagnosis: of congenital malformations (screening should be done by detailed ultrasound and measurement of alfa fetoprotein at 18 weeks).

III- LABOUR AND DELIVERY “The risk of developing a seizure during labor is 9 times that during the rest of pregnancy”. Management of women with epilepsy upon labor and delivery:  Check levels of AEDs.  Inform all health care providers that the patient has epilepsy.  Consider seizure prophylaxis with intravenous benzodiazepines or phenytoin.

Management of a pregnant patient in status epilepticus: Establish the ABCs, and check vital signs. Assess the fetal heart rate. Rule out eclampsia. Administer a bolus of lorazepam (0.1 mg/kg, ie, 5-10 mg) at no faster than 2 mg/min.

Generalized tonic clonic Seizures GTCSs needs aggressive interference because of the high risk for the mother and fetus, especially if they progress to status epilepticus. Oxygen should be administered to the patient and she should be placed on her left side to increase uterine blood flow and decrease the risk for maternal aspiration. Emergency C.S. should be performed when repeated GTCSs cannot be controlled during labor or when the mother is unable to cooperate. Any lady having a seizure during labour must be observed closely for the next 72 hours.

Vitamin K 10 mg a day orally is to be given to mother in the last two weeks. There is no contraindication for breastfeeding. Infant is given injection vitamin K 1mg IM at birth to prevent neonatal hemorrhage due to decreased vit K dependent clotting factors. The infant may be drowsy. Readjustment of the anticoagulant dosage is necessary and to bring down the dose to the pre pregnant level by 4-6 weeks postpartum. Steroidal contraceptives are better to be avoided due to hepatic microsomal enzyme induction. The risk of having epilepsy of an infant born to a mother with a seizure disorder is four times higher compared to a normal one.

NURSING MANAGEMENT 1.Risk for growth retardation related to epilepsy 2.Risk for pre-term labor 3.Knowledge deficit related to the disease condition 4.Anxiety related to hospitalization 5.Impaired tissue perfusion related to headache, slurred speech  Risk for injury related to epileptic episode 6.Fear related to the possibility of seizure 7.Ineffective individual coping related to stress imposed by epilepsy 8.Deficient knowledge related to epilepsy and its control.

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