Physiologic changes
Eclampsia and epilepsy are the leading causes of seizures in pregnancy. Eclampsia is a pregnancy-induced condition, caused by the endothelial cell dysfunction of pre-eclampsia. Many physiologic changes in pregnancy may increase seizure risk for other women, particularly those with epilepsy. Chronic respiratory alkalosis, stress, anxiety, and sleep deprivation may lower the seizure threshold. For women taking antiepileptic drug (AED) therapy, nausea and vomiting may decrease drug absorption. Increases in maternal weight, plasma estrogens, and total body water may decrease AED levels through expansion of volume of distribution, decreased protein binding, and increased AED clearance [1–3]. Most important of all is maternal noncompliance with AED therapy, which occurs in up to two-thirds of women with epilepsy [4] and is responsible for 20% of status epilepticus [5].
Evaluation and investigation of the pregnant woman with a seizure should follow the same general principles as for any adult, with attention paid to the diagnostic possibility of eclampsia.
Epidemiology
A seizure in pregnancy is most likely to be secondary to epilepsy or eclampsia, which occur in 30–60/10,000 [1,6,7] and 5/10,000 pregnancies [8].
Etiology/pathophysiology
Epilepsy results from a genetically or acquired brain disorder. Eclampsia is associated with vasomotor instability, hypercoagulability, and inflammation of pre-eclampsia. Other causes of seizures may be structural or metabolic.
General course in pregnancy
Increased seizure frequency occurs in 15–30% of pregnant women with epilepsy [1,9,10] but status epilepticus is no more frequent and is rare (<1%) [2]. Among women with epilepsy, seizure frequency has not been associated with seizure type, duration of epilepsy or seizure frequency in a previous pregnancy [1].
Clinical presentation
Signs and symptoms
A seizure is a sudden change in behavior as a result of excessive neuronal activation in the cerebral cortex. Status epilepticus is a single unremitting seizure or frequent recurrent seizures without interictal recovery of consciousness lasting for at least 30 minutes; however, status should be assumed if a woman has seized for 10 minutes [11,12]. Eclamptic seizures are indistinguishable (clinically or by electroencephalogram (EEG) criteria) from other types of generalized tonic-clonic seizures, but there are some unique features (Box 45.1).
Diagnosis
A detailed description should be sought of the pre-“seizure” period, “seizure” itself, and post-“seizure” period in order to guide the differential diagnosis (Box 45.2). Specific points to verify include: signs or symptoms of pre-eclampsia; noncompliance with AED in women with epilepsy; history of childhood seizures; illicit, prescription and over-the-counter drug use; and intrapartum anesthesia (if relevant). The physical exam should be focused on “ABCs” of assessment, establishing maternal and fetal well-being, ruling out complications (e.g. aspiration) and ascertaining the cause of the suspected seizure. Assessment of fetal heart rate (FHR) and pattern must also be included.
Box 45.1 Characteristics of eclampsia
Timing
- By definition, occurs after 20 weeks gestation, but presentations before 20 weeks have been reported rarely
- Women may seize antepartum (38%, and usually at preterm gestational ages), intrapartum (18%) or post partum (44%, usually within 48 hours of delivery, although reports exist of eclamptic seizures occurring as late as 14 days post partum)
- The majority (75%) of eclamptic seizures that occur during labor and in the postpartum period are observed in women who deliver at term
Symptoms and signs
- Self-limited, generalized tonic-clonic event that lasts less than 3–4 minutes
- May occur in the absence of antecedent pre-eclampsia, significant hypertension or maternal symptoms; prior to their first eclamptic convulsion, 40% of women do not have both hypertension and proteinuria (i.e. the traditional definition of pre-eclampsia) and 40% are asymptomatic
Laboratory evaluation and diagnostic testing
Basic investigations are the same as for the nonpregnant patient (Table 45.1). These detailed investigations and neurology consultation may be useful in any case of eclampsia but are definitely indicated for:
Table 45.1 Investigations for a woman with a seizure in pregnancy
| Investigation | Remarks |
| Needed in all women | |
| Needed in all women Bloodwork | “Pre-eclampsia laboratory markers”: CBC, creatinine, uric acid, AST, ALT, LDH, bilirubin Other biochemistry: electrolytes, glucose, calcium, magnesium Toxicology screen |
| Urinalysis | Urinary protein quantification |
| May be needed depending on history and physical exam | |
| Neuroimaging | CT scan or MRI of head |
| EEG | Without, and possibly with, sleep deprivation |
| Lumbar puncture∗ | Opening pressure, minimal CSF parameters†: cell count, glucose, protein, gram stain and culture |
| ECG +/− Holter monitor | Rule out arrhythmia |
| Echocardiogram | Rule out valvular heart disease |
| ∗After excluding increased intracranial pressure. | |
| † Other tests should be guided by clinical situation (e.g. cryptococcal antigen in a woman with known HIV). | |
ALT, alanine transaminase; AST, aspartate transaminase; CBC, complete blood count; CSF, cerebrospinal fluid; ECG, electrocardiogram; EEG, electroencephalogram; LDH, lactate dehydrogenase.
- a first seizure that occurs without the other characteristic features of eclampsia (i.e. hypertension, proteinuria or end-organ complications), even in the presence of another clear identifiable precipitant (e.g. hypoglycemia) [13,14]
- a seizure that has focal onset, is of a nongeneralized nature or is associated with focal neurologic findings, sustained obtundation or loss of consciousness
- recurrent/persistent eclamptic seizures
- a seizure in a patient with known epilepsy that is not consistent with their usual pattern or has no clear precipitant.
Box 45.2 Causes of a seizure in pregnancy
Pregnancy-induced causes
- Eclampsia
- Complications of regional anesthesia†
Other causes of seizure∗
- Epileptic seizure (recurrent or de novo)
- CNS infection
- Metabolic:
- hypoglycemia
- extreme hyperglycemia
- hyponatremia
- hypocalcemia
- uremia
- hepatic encephalopathy
- hypoglycemia
- Tumor/mass (e.g. AVM, cerebral meningioma)∗
- AED withdrawal or overdose
- Illicit stimulant drug use
- Alcohol or drug withdrawal
- Trauma (e.g. subdural hematoma)
- Hemorrhage (e.g. subarachnoid or intracerebral hemorrhage)∗
- Thromboembolism (e.g. cerebral sinus thrombosis)∗
- Psychogenic nonepileptic seizures (“pseudo-seizures”)
AED, antiepileptic drugs; AVM, arteriovenous malformation; CNS, central nervous system; SAH, subarachnoid hemorrhage.
†For example, bacterial or aseptic meningitis, “high” spinal anesthesia or intravascular injection of local anesthetic.
∗Causes more likely to occur or worsen in pregnancy.
Detailed investigations may consist of one/more of the following.
- Either computed tomography or magnetic resonance imaging, both of which are acceptable. Computed tomography (CT) of the head is abnormal in approximately one-third of women with typical eclampsia. Typical changes are hypodensities in the cerebral cortex and subcortical white matter, usually localized to the posterior parietal and occipital areas, but also in the watershed area between the anterior, middle and posterior cerebral arteries [15]. Magnetic resonance imaging (MRI) demonstrates similar changes (characterized by high signal intensity on T2-weighted scans), but in a higher proportion (i.e. 46%) of women with eclampsia.
Magnetic resonance imaging is preferable if there is a strong suspicion of a posterior fossa lesion or cerebral venous thrombosis, a clinical stroke (particularly if the CT head is normal) or no obvious cause of a seizure and the brain CT is normal. Neither CT nor MRI is associated with significant fetal radiation exposure and neither has been associated with adverse fetal effects [16]. The choice of technique will depend in part on local availability.
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