eMedicine Specialties > Neurology > Seizures and Epilepsy

Preeclampsia and Eclampsia

Author: Aashit K Shah, MD, Associate Professor of Neurology, Wayne State University; Program Director, Clinical Neurophysiology Fellowship, Department of Neurology, Detroit Medical Center
Contributor Information and Disclosures

Updated: Jun 18, 2009

Introduction

Background

Preeclampsia/eclampsia is a complex pregnancy-specific hypertensive syndrome of reduced organ perfusion related to vasospasm and activation of the coagulation cascade affecting multiple systems. The nervous system is commonly affected and is a cause of significant morbidity and death in these women.¹

Preeclampsia and eclampsia are not distinct disorders but are differentiated according to their clinical symptoms. The mildest disorder in this continuum is pregnancy-induced hypertension (PIH). In preeclampsia, hypertension and proteinuria are present, and when convulsions occur in addition to these signs, the condition is referred to as eclampsia. Although seizures define the condition of eclampsia, other neurologic findings may be observed earlier in the continuum of PIH/preeclampsia/eclampsia. The progression from mild PIH to preeclampsia and eclampsia may not occur in all women. In a prospective study at the author's center, as many as 28% of the women with a diagnosis of eclampsia did not have a diagnosis of preeclampsia prior to seizures.²

The hypertensive disorders of pregnancy can be classified as follows:

• Chronic hypertension
• Preeclampsia-eclampsia
• Preeclampsia superimposed on chronic hypertension
• Gestational hypertension: (1) transient hypertension of pregnancy if preeclampsia is not present at the time of delivery and blood pressure returns to normal by 12 weeks postpartum (a retrospective diagnosis) or (2) chronic hypertension if the elevation persists.

Chronic hypertension is defined as hypertension that is present and observable before pregnancy or that is diagnosed before the 20th week of gestation. Hypertension is defined as a blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic. Hypertension that is diagnosed for the first time during pregnancy and that does not resolve postpartum is also classified as chronic hypertension.

Preeclampsia-eclampsia is a pregnancy-specific syndrome that occurs after 20 weeks’ gestation (or earlier in the case of trophoblastic diseases such as hydatidiform mole or hydrops). It is determined by increased blood pressure (gestational blood pressure elevation) accompanied by proteinuria. Gestational blood pressure elevation is defined as a blood pressure >140 mm Hg systolic or >90 mm Hg diastolic in a woman who was normotensive before 20 weeks’ gestation. In the absence of proteinuria, the disease is highly suspected when increased blood pressure appears accompanied by the following symptoms: headache, blurred vision, and abdominal pain, or by abnormal laboratory test results, specifically low platelet counts and abnormal liver enzyme values.

In the past, it has been recommended that an increment of 30 mm Hg systolic or 15 mm Hg diastolic blood pressure be used as a diagnostic criterion, even when absolute values remain <140/90 mm Hg. This definition has not been included in our criteria, because the only available evidence shows that women with blood pressures fitting this description are not likely to have increased adverse outcomes. Nonetheless, it is the collective clinical opinion of this panel that women who have a rise of 30 mm Hg systolic or 15 mm Hg diastolic blood pressure warrant close observation, especially if proteinuria and hyperuricemia (uric acid ≥6 mg/dL) are also present.

The diagnosis of preeclampsia superimposed on chronic hypertension is a difficult one. It is suspected in the following cases:

• In women with hypertension and no proteinuria early in pregnancy (<20 weeks’ gestation), new-onset proteinuria, defined as the urinary excretion of ≥0.3 g protein in a 24-hour specimen
• In women with hypertension and proteinuria before 20 weeks’ gestation any of the following are seen:
  • Sudden increase in proteinuria
  • Sudden increase in blood pressure in a woman whose hypertension has previously been well controlled
  • Thrombocytopenia (platelet count <100,000 cells/mm³)
  • Increase in alanine aminotransferase or aspartate aminotransferase level to abnormal levels¹

Pathophysiology

As mentioned above, preeclampsia/eclampsia is a multisystem disorder and also affects the fetus when it occurs prior to delivery. The cardiovascular system is routinely involved, with hemodynamic changes resulting from severe hypertension that may lead to cardiac failure or pulmonary edema. The kidneys also are commonly affected, with resultant proteinuria and decreased glomerular filtration rate, which may lead to acute tubular necrosis and renal failure in severe cases. Hematologic changes related to the consumption of platelets and clotting factors resulting in intravascular coagulation may occur, at times associated with evidence of intravascular erythrocyte destruction. Abnormal liver function test results with elevation of liver enzyme levels can be observed commonly, but, in rare instances, spontaneous hepatic rupture may ensue. Involvement of the brain may cause convulsions, coma, altered mental status, cortical blindness, and other manifestations of focal brain dysfunction.

Risk factors for preeclampsia include (1) a previous history of preeclampsia, (2) primiparity, (3)obesity, (4) family history of preeclampsia, (5) multiple pregnancies, and (6) chronic medical conditions such as long-term hypertension or diabetes. Paradoxically, cigarette smoking reduces the risk. Thrombophilia, an inherited tendency to overactive coagulation, may also be a consideration.³

The exact etiology of preeclampsia/eclampsia is not known. Current thinking is that the problem starts with the placenta and begins early during pregnancy. Fetal or uterine participation apparently are not crucial because this condition is identified in abdominal pregnancy and hydatidiform mole. During later stages of pregnancy, there is extensive remodeling of maternal spiral arteries as the placenta requires increasing access to the maternal blood supply. In women with toxemia, the trophoblastic implantation is abnormal, resulting in lower placental perfusion.¹ The resultant hypoxia secondary to placental hypoperfusion induces release of soluble vasoactive substances and reactive oxygen species into the maternal circulation, which can cause endothelial dysfunction and generalized systemic inflammatory response. This, in turn, can cause systemic hypertension by impairing renal pressure natriuresis and increasing peripheral resistance.⁴

The candidates for such effects are soluble factors that can be released into maternal circulation causing widespread effects. One such molecule is vascular endothelial growth factor (VEGF)–1, also known as sFlt1 (soluble fms-like tyrosine kinase 1), and another one is neurokinin B.³ This leads to widespread vasospasm, and this vasospasm is considered to be central to the condition. Vasospasm leads to increased resistance to blood flow with resultant hypertension. This may also induce further endothelial damage and leakage of platelets and fibrinogen into the subendothelial space. These changes ultimately lead to surrounding tissue hypoxia, resulting in necrosis or hemorrhage in multiple end organs.

Usually, pregnant women develop marked reduction in peripheral vascular resistance. They also develop refractoriness to infused vasopressors, such as angiotensin II.⁵ These hemodynamic changes are reversed in preeclampsia/eclampsia. This may be due to decreased vascular responsiveness mediated, in part, by vascular endothelial synthesis of prostaglandins or similar substances. Decreased production of prostacyclin and increased synthesis of thromboxane-A2 in PIH may result in vasoconstriction.⁶ In addition, decreased production or release of nitric oxide, a potent vasodilator, may contribute to the development of or aggravate the preeclampsia/eclampsia syndrome.⁷ In a prospective observational study, amniotic fluid concentration of endothelin was found to be elevated by the second trimester in women who later developed preeclampsia.

Frequency

United States

The incidence of preeclampsia is about 5% of pregnancies; the range is 5-10%. The incidence of eclampsia is considered to be about 5-7 cases per 10,000 deliveries.

International

The incidence of preeclampsia and eclampsia in the developed countries of North America and Europe is similar to those of the United States. On the other hand, incidence of eclampsia in developing nations varies widely, ranging from 1 case per 100 pregnancies to 1 case per 1700 pregnancies.

Mortality/Morbidity

• Although eclampsia is a rare complication of pregnancy, approximately 50,000 women worldwide are estimated to die annually because of eclampsia.
• The reported maternal mortality rate ranges from 1-20%.
• The perinatal mortality rate of neonates born to eclamptic mothers ranges from 1.3-3%.

Race

• Preeclampsia/eclampsia syndrome is more common in blacks than in Hispanics.
• Hispanic women are more likely to be affected by this syndrome than white women.
• Higher incidences of the syndrome in the developing world may be related to racial differences, but effects of other environmental and social factors cannot be underestimated.

Age

Preeclampsia/eclampsia is more likely to occur in women at either extreme of reproductive life.

• A young nulliparous woman is more likely to experience the condition.
• Similarly, a multiparous woman older than 35 years is more likely to be affected.
• Other risk factors include multiple pregnancies, hydatidiform mole, and extrauterine pregnancy.

Clinical

History

This discussion is restricted to the neurological manifestations of preeclampsia/eclampsia syndrome. The syndrome of preeclampsia/eclampsia usually progresses in stages of worsening elevation of blood pressure, development of generalized edema, and headache followed by seizure; however, it can worsen very quickly, and a patient can develop serious neurologic and systemic complications in a matter of hours. On the other hand, some women may have seizures in the setting of moderate elevation of blood pressure without developing any other symptoms.

• Headache: The most common neurologic symptom in preeclampsia/eclampsia is headache; however, it is not an essential part of the clinical presentation.
  • Headache occurs in about in 75% women with seizures (eclampsia) and always precedes the seizure.⁸ At the time of the seizures, headache is present for more than a day in most women. Headache can be bitemporal, frontal, occipital, or diffuse. Most women describe the headache as pulsating pain, but pain associated with feelings of pressure or sharp pain can also be present. The typical feature of the headache is that it is progressive and does not respond to routine over-the-counter remedies.⁹ In a minority of women, it is associated with photophobia or sonophobia, nausea, and rarely, vomiting. A new onset of progressive headache in a pregnant woman should alert her physician to the possibility of preeclampsia or eclampsia.
  • Rarely, sudden explosive headache can occur and at times may be indicative of subarachnoid hemorrhage. A recent report has suggested that a small amount of subarachnoid hemorrhage over the cerebral convexity can occur in preeclampsia/eclampsia. However, it appears to carry a relatively benign long-term prognosis.¹⁰
• Seizures: Convulsions are the other most common feature of this syndrome. Convulsions are the most common neurologic manifestation in eclampsia because the occurrence of convulsions confirms the diagnosis of eclampsia. Convulsions are usually generalized tonic-clonic in nature. Usually a brief single seizure occurs. Multiple seizures can also occur; however, status epilepticus is rare. Partial seizures or complex partial seizures can also occur.² The seizures can occur prepartum, intrapartum, or postpartum. If the seizure occurs postpartum, it usually occurs within the first 24 hours after delivery; however, late postpartum eclamptic convulsions are by no means rare and have been reported as late as 23 days postpartum.^11,8
• Visual disturbances: Visual changes are common in preeclampsia/eclampsia. The most common symptom is blurring of vision. The visual disturbances are ominous and may indicate impending seizure. Blindness in women with eclampsia is rare and can be due to involvement of the occipital cortex or retina. Cortical blindness usually follows or heralds seizures. Again, it can occur in isolation without seizures. This demonstrates involvement of the brain in women with severe preeclampsia without seizure (ie, eclampsia). The blindness is usually transient and resolves completely within a few hours, but it may last longer and rarely be permanent.¹² The other possibility is retinal detachment due to severe hypertension resulting in blindness; however, this is usually unilateral. A case of central retinal vein occlusion in association with preeclampsia has been reported.¹³
• Coma: Coma is a dreaded complication in eclampsia. Most women lapse into coma following a convulsion or repeated convulsions. Others may have not had a seizure prior to coma. However, comatose state without observed seizure cannot be classified as eclampsia by most recent diagnostic criteria. Coma may be a result of intracerebral hemorrhage that, at times, may dissect into the ventricular system or over the surface of the brain, creating a massive subarachnoid hemorrhage. Coma can also follow a sudden rise in blood pressure, with resultant cerebral edema without hemorrhage.
• Symptoms of focal brain dysfunction: Other symptoms, such as hemiparesis and monoparesis, can also be observed in eclampsia if a region of the brain is malfunctioning. Other than cortical blindness, focal brain dysfunctions are rare.
• Other systemic symptoms: Preeclampsia/eclampsia is a systemic disorder, and nonneurologic symptoms are more common than neurologic symptoms in most women. Some women may be completely asymptomatic despite a markedly elevated blood pressure; however, they need to be monitored and cared for as carefully as other women with symptoms.¹⁴
  • Edema: Generalized edema is a common, but not an essential, feature of this syndrome. Swelling of feet and even hands is common in women during late pregnancy. Differentiating this edema from pathological edema is sometimes difficult. Edema of the hands and face should be regarded as pathological edema.
  • Weight gain: Fluid retention is a physiologic consequence of pregnancy; however, excessive fluid retention in preeclampsia/eclampsia causes sudden gain in weight. This is again considered a warning sign for development of preeclampsia.
  • Abdominal pain: The liver is commonly affected in this syndrome. Stretching of the capsule of the liver or ischemia results in pain in the right upper quadrant or epigastrium. Subcapsular hematoma or rupture of the liver may cause excessive pain in the area.

Physical

Physical examination is important in preeclampsia/eclampsia, both for diagnosis of the condition as well as for monitoring its progress and effects of the interventions.

• Blood pressure: Elevation of blood pressure is essential for the diagnosis of preeclampsia/eclampsia syndrome. Blood pressure in excess of 140/90 mm Hg after 20 weeks of gestation (or earlier in case of trophoblastic disease) is accepted as high. However, relative hypertension can be difficult to define. In the past, it has been suggested that elevation of systolic blood pressure by 30 mm Hg and diastolic blood pressure by 15 mm Hg from baseline can be used even of absolute values remain <140/90 mm Hg, a requisite for the diagnosis of preeclampsia or eclampsia.¹ In the majority of women with eclampsia, this is not an issue because the blood pressure elevation is extreme.
• Edema: Generalized edema is also common in this condition. Pitting edema of feet, legs, hands, and face can be observed. Nevertheless, women without edema may still have extremely high blood pressure or can experience seizures. Similarly, edema is common with normal pregnancy and is not a very helpful clinical sign to distinguish preeclampsia from normal pregnancy. Hence, it is no longer used as a marker.¹
• Abdominal tenderness: Swelling of liver or liver ischemia can cause tenderness of the organ, as mentioned above.
• Neurologic examination: Findings of the neurologic examination are normal in most women or show only subtle abnormalities.
  • Hyperreflexia: The most common finding on neurologic examination in women with eclampsia is hyperreflexia. However, differentiating this hyperreflexia from physiologic hyperreflexia observed in young individuals may be difficult. At times, the only way to diagnose the presence of hyperreflexia is by examining the woman later on and making the distinction retrospectively.
  • Blindness: Blindness may herald seizure in severe preeclampsia or may follow the seizure. In cases of cortical blindness, the findings on eye examination are completely normal, including pupillary light reflex. The blindness is transient in most patients and resolves completely.¹⁵ The patient may develop denial of the blindness, known as Anton syndrome. Involvement of the parieto-occipital junction area may cause Balint syndrome.^8,16
  • Funduscopic examination: Funduscopic examination may reveal papilledema and vasoconstriction. In rare instances, it may show focal hemorrhage or retinal detachment.
  • Focal neurologic findings: Depending on the extent of the brain involvement and location of the abnormalities, examination of the motor or sensory functions or deep tendon reflexes may reveal some abnormalities.
  • Coma: Depending on the severity of the underlying brain involvement, the neurologic findings in a comatose patient vary. The patient may be completely unresponsive or may demonstrate posturing.
  • Cognitive dysfunction: Memory deficit is rather common in women with eclampsia. Other deficits of higher cortical function can be observed occasionally, such as Balint syndrome, Anton syndrome, dyscalculia, confusion, or disorientation. These deficits are transient in nature and quickly disappear in tandem with improving toxemia.⁸

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