DR MUHAMMAD AKRAMMATERNITY AND CHILDREN

HOSPITALMAUSADIA, JEDDAH

Definition and Incidence

Epilepsy is recurring spontaneous seizures due to sudden excessive and disordered electrical discharge from the neurones of the Cerebral cortex.

7% of epileptic women become pregnant epilepsy affects about 0.5-1% of pregnant

women.

Epilepsy can be partial or generalized.

Classification Of Epilepsy

A- Partial Seizures (Focal Seizures): This is the commonest type and is subcategorized as :

1-Simple Partial Seizures (Jacksonian epilepsy): The affected woman does not lose consciousness but may experience confusion, tingling, or odd mental and emotional events. Such events may include mild hallucinations, or extreme responses to smell and taste.

After the seizure, the patient usually has temporary weakness in certain muscles.

Classification Of Epilepsy

2- Complex Partial Seizures (>50% in adults):They can result in loss of judgment, involuntary uncontrolled behavior & loss of consciousness. Prior to the actual seizure, some people may experience a warning aura, which can be an odd odor, a feeling of warmth, or a visual or auditory hallucination. They then may lose consciousness briefly and appear to others as motionless with a vacant stare. After a few seconds, some may begin to perform repetitive movements, such as chewing or smacking of lips. Episodes usually last no more than two minutes.

Ocassionally a simple or complex partial seizures evolve into secondarily generalized seizures. The progress may be so rapid that the partial stage is not even noticed.

Classification Of Epilepsy

B- Generalized SeizuresThey occur in more diffuse areas of the brain and they have more serious effect on the patient. They are further subcategorized as follows:

1-Tonic-Clonic (Grand Mal) Seizures:a-The tonic phase: muscles suddenly contract, causing the patient to fall and lie rigidly for about 10 to 30 seconds. Some people experience aura; most, lose consciousness without warning. If the throat or larynx is affected, stridor occurs when the patient inhales.

b-The clonic phase: Seizure is said to enter this phase when the muscles begin to alternate between relaxation and rigidity. After this phase, the patient may lose bowel or urinary control.

The seizure usually lasts a total of two to three minutes, after which the patient remains unconscious for a while and then awakens to confusion and extreme fatigue.

Classification Of Epilepsy

2-Absence (Petit Mal) Seizures: Petit mal or absence seizures are brief (three to 30 seconds) losses of consciousness and may consist of only a short cessation of physical movement and loss of attention. Such seizures may pass unnoticed by others. About 25% of patients with petit mal develop grand mal seizures

Classification Of Epilepsy

C- Other Seizures:1- Atonic (Akinetic) Seizures. A person who has an atonic (or

akinetic) seizure loses muscle tone. Sometimes it may affect only one part of the body so that, for instance, the jaw slackens and the head drops. At other times, the whole body may lose muscle tone, and the person can suddenly fall.

2- Simply Tonic or Clonic Seizures. Seizures can also be simply tonic or clonic. In tonic seizures, the muscles contract and consciousness is altered for about 10 seconds, but the seizures do not progress to the clonic phase. Clonic seizures, which are very rare, occur primarily in young children, who experience spasms of the muscles but not their tonic rigidity.

3- Myoclonic. Myoclonic seizures are a series of brief jerky contractions of specific muscle groups, such as the face or trunk.

Classification Of Epilepsy

4-Gestational epilepsy: Some patients experience their first seizures during pregnancy. This can be a result of true gestational epilepsy, a rare syndrome of seizures occurring only during pregnancy. Patients with this syndrome have a variable presentation with single or multiple seizures in one or more of their pregnancies. It can also be a manifestation of epilepsy that may extend beyond the pregnancy.

The workup of these patients should involve a neurologic examination, consultation with a neurologist, CBC count, chemistry panel (particularly for electrolytes), head MRI versus CT scan, and EEG. The differential diagnosis should include eclampsia and any possible etiology considered in the nonpregnant patient, including stroke, electrolyte abnormalities, tumor, trauma, drugs/withdrawal, and epilepsy

Effects Of Pregnancy On EpilepsyUnpredictable

1-Seizure frequency may increase: due to:-Enhanced metabolism & increased drug clearance associated withpregnancy can result in decreased serum drug concentration.-Increased volume of distribution of the AED.-Increased serum binding proteins.-Decreased or non-compliance with medication.-Sleep deprivation, hormonal changes of pregnancy (high E), and associated psychological and emotional stress of pregnancy: all

increase threshold for seizures.-Nausea and vomiting.

Effects Of Pregnancy On Epilepsy (Cont.)

2-Seizure frequency may decrease:Due to improved compliance with drug regimen in some patients.

3-Seizure frequency may remain unchanged.

Effect Of Epilepsy On Pregnancy

Data on 1st trimester losses, PROM, ante-partum hemorrhage, operative vaginal delivery and CS are inconclusive.

Increased incidence of IUGR, cognitive dysfunction, microcephaly and perinatal mortality (1.2 - 3 times normal).

Increased incidence of congenital malformations.

Effect Of Epilepsy On Lactation

No studies on the effects of AED on either quantity or quality of breast milk.

Breast feeding should be stopped if obvious sedation develops in an infant and is likely to relate to the presence of AED in breast milk.

Effects Of Epilepsy On Fetus And Neonate

1-There is increased risk for infants of epileptic mothers to have epilepsy. The risk of neonatal susceptibility depends on:

Nature of the mother’s seizure disorder. Genetic factors. Seizures arises during pregnancy. Metabolic & toxic consequences of seizures and AEDs.

2-Increase perinatal morbidity.

Table 1. Antiepileptic Drug Exposure Through

Breast Milk Pennell PB, 2004___________________________________

AED Breast milk/maternal conc Adult half-life NN half-life

______________________________________________________________________Carbamazepine 0.4–0.6 8–25 8–28Phenytoin 0.18–0.4 12–50 15–105Phenobarbital 0.36–0.6 75–12645–500Ethosuximide 0.8–0.9 32–60 32–40Primidone 0.7–0.9 4–12 7–60Valproic acid 0.01–0.10 6–18 30–60Lamotrigine 0.6 —— ___Topiramate 0.69–0.86 —— ___Zonisamide 0.41–0.93 63 61–109Levetiracetam 3.09 —— ___

MANAGEMENTI-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.

MANAGEMENTI-Preconceptional Care:

C-Measurement of the free unbound anti-epileptic drug level in maternal serum.

D- Preconceptional folate supplementation: 5 mg daily.

E- No trial to stop AED unless the patient is seizure free at least for 2 years. The AED dose should be tapered till stopped completely at least 6 months prior to any planned pregnancy to provide some reassurance that seizures are not going to recur.

II-ANTENATAL CAREA-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.

II-ANTENATAL CARE

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).

II-ANTENATAL CARE (CONT.)

G-Vitamin K: Oral 20mg daily is prescribed from 36 weeks until delivery to mothers taking hepatic enzyme-inducing drugs (phenytoin, phenobarbitone, primidone, carbamazepine and topiramate - Not necessary with sodium valproate).

Be aware of the nature of the AED you are using whether it is a hepatic enzyme inducing or not. Most of the newer AEDs are not enzyme inducers).

III-LABOR AND DELIVERY (CONT.)

“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.

III-LABOR AND DELIVERY (CONT.)

Manage seizures acutely with intravenous benzodiazepines (1-2 mg of diazepam), then load phenytoin (1 g loaded over 1 h).

Labor management should be based on routine standards of care.

Start administration of vitamin K1 for the infant, and send the cord blood for clotting studies.

III-LABOR AND DELIVERY (CONT.)

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.

III-LABOR AND DELIVERY (CONT.)

Load phenytoin (20 mg/kg, ie, 1-2 g) at no faster than 50 mg/min, with cardiac monitoring.

If this is not successful, load phenobarbital (20 mg/kg, ie, 1-2 g) at no faster than 100 mg/min.

Check laboratory findings, including electrolytes, AED levels, glucose, and toxicology screen.

If fetal testing results are nonreassuring, move to emergent delivery.

III-LABOR AND DELIVERY

The majority of women who have epilepsy have a safe vaginal delivery without seizure occurrence; provided, the AED is taken before and throughout labor.

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.

III-LABOR AND DELIVERY (CONT.) 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.

Obstetric analgesia may be used to allow for rest before delivery. Pethidine should never be used because it is metabolised to norpethidine, which is epileptogenic. Diamorphine is an option. Few cases of postpartum seizures were reported following epidural analgesia.

III-LABOR AND DELIVERY (CONT.) During labor, oral absorption of AEDs may be

inappropriate and any vomiting might complicate the situation. PB, PHT, and VPA can be given IV at the same maintenance dosage. Convulsive seizures and repeated seizures during labor should be treated promptly with parenteral lorazepam or diazepam.

Benzodiazepines, in large doses, can cause neonatal cardiac and respiratory depression; therefore, close monitoring for these neonates is mandatory.

AAN 2009: New Guidelines Released on Pregnancy with Epilepsy

Upto Date 2011 The management of epilepsy in

pregnancy BJOG: An International Journal of

Obstetrics & GynaecologyVolume 116, Issue 6, pages 758–767, May 2009