AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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.

(For a CME activity, see Preeclampsia May Increase Risk for End-Stage Renal Disease.)

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Dural sinus thrombosis
Epilepsy presenting during pregnancy or in the postpartum period
Brainstem syndromes
Hypertension and stroke
Postpartum cerebral angiopathy

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• CBC count
• • CBC count is essential to rule out CNS infection manifesting as seizures.
  • Evaluating thrombocytopenia, a potentially dangerous complication of pregnancy-induced toxemia, is also helpful. Another condition that may be associated and may be a part of the syndrome is hemolytic anemia, elevated liver enzymes, and low platelet, also known as HELLP.
  • Anemia is common in women with eclampsia and is believed to be a contributing factor.
• Peripheral smear: This study is ordered to evaluate for microangiopathic hemolytic anemia with destruction of RBCs.
• Urinalysis
• • Proteinuria is common (usually >2+). In preeclampsia/eclampsia, it should be present in a repeat study at least 6 hours later.
  • On 24-hour urine analysis, most women with eclampsia have significant proteinuria (>300 mg/24 h).
• Serum studies: Several studies are useful.
• • Serum blood urea nitrogen (BUN) and creatinine measurements are necessary to evaluate and monitor kidney function.
  • The liver is another organ affected in eclampsia. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin measurements are helpful. The most common abnormality is elevation of serum AST.

Imaging Studies

• CT scanning of the brain
• • CT scanning of the brain is useful in diagnosing cerebral hemorrhage, a rare complication in eclampsia. However, rarely preeclampsia/eclampsia is associated with primary nonaneurysmal subarachnoid hemorrhage.¹⁰ This is usually localized to a small area over the cerebral convexity, and the amount of blood is small. This is in contrast to the usual finding in aneurysmal bleed, which shows blood basal brain cisterns (see Media file 5).
  • CT scanning is also helpful in diagnosis of other causes of cerebral hemorrhage, such as arteriovenous malformation, cerebral tumor, and calcification representing a brain tumor or old infection, such as tuberculosis, cysticercosis, or other fungal/parasitic infections.
  • Characteristic findings of eclampsia in CT scanning include white matter hypodensities, mainly affecting cerebral white matter of the occipital/parietal lobes or the deep white matter of internal/external capsules.¹⁷ (See Media file 1.) These changes are transient and may resolve over a few days.
• MRI of the brain
• • MRI is more sensitive than CT scanning of the brain in identifying changes related to eclampsia.
  • The characteristic findings include hyperintense lesions on T2-weighted, fluid attenuation inversion recovery (FLAIR) or proton-weighted sequences affecting the white matter and adjacent gray matter of the occipital/parietal lobes; however, deep white matter structures, basal ganglia, and white matter of the frontal or temporal lobes and brain stem can also be affected.^{18, 19}(see Media files 2-4).
  • T1-weighted images are usually unremarkable or may show subtle hypodensities in the same structures.
  • DWI and apparent diffusion coefficient (ADC) mapping are new techniques to evaluate acute cerebral ischemia. In patients with eclampsia, DWI MR images or ADC maps usually show no abnormalities suggestive of ischemia (cytotoxic edema). The changes seen on T2-weighted images representing vasogenic edema are reversible. In cases in which DWI MRI show findings of restricted diffusion suggestive of cytotoxic edema, persistent imaging abnormalities suggesting permanent brain damage may be observed on a follow-up MRI. These changes may affect only small areas compared with the much larger area of involvement with vasogenic edema that is reversible. Thus, MRI combining T2-weighted images and DWI ADC images can be very useful to determine the extent of likely permanent cerebral injury.¹⁸
  • Magnetic resonance (MR) angiography findings may be normal or may show reversible cerebral vasospasm.
  • MR venography findings are usually normal and are helpful in excluding the possibility of dural sinus thrombosis, an important differential diagnosis.
  • Combination of routine MRI with T1- and T2-weighted images, DWI, and MR venography is very helpful in suspected cases of eclampsia.¹⁸ Routine MR imaging with T1- and T2-weighted images helps in confirming the diagnosis of eclampsia by showing characteristic changes. DWI helps to exclude the possibility of acute stroke (ie, absence of abnormal signal on DWI in the same region showing hyperintense lesion on T2-weighted images). Recently, reports have indicated that some of the lesions observed on T2-weighted images are hyperintense on DWI and show restricted diffusion. This, in turn, suggests that some lesions may result from cytotoxic edema and result in irreversible damage and small areas of ischemic infarcts. This has been shown on repeat MRI. In addition, MR venography helps to demonstrate patency of dural sinuses, helping to eliminate the possibility of sinus thrombosis.
  • MRI of the brain should thus be preferred over CT scanning in women with suspected eclampsia.
  • Location of imaging abnormalities on basis of T2-weighted MR imaging in decreasing frequency is as follows: high parietal, high posterior frontal, lateral occipital, occipital pole, medial occipital, basal ganglia, anterior frontal, lateral temporal, internal capsule, cerebellum, external capsule, corona radiata, inferior parietal, brain stem, medial temporal lobe, and thalamus.⁸
• Cerebral angiography: Cerebral angiography should not be performed routinely. It shows focal/segmental cerebral vasoconstriction. The venous phase of the study also helps to show normal flow pattern in dural sinuses, again helping to exclude sinus thrombosis.
• Transcranial Doppler study: This is a research tool used in the evaluation of eclampsia. It shows an increased velocity of blood flow in the middle cerebral artery, which is reversible. The changes tend to parallel the severity of the clinical syndrome.²⁰
• Ultrasonography: Abdominal ultrasonography may be needed to evaluate for hepatic abnormalities or hemorrhage. It should be performed in women with abdominal tenderness.

Procedures

• Amniocentesis may be necessary prior to delivery to determine fetal lung maturity.

Histologic Findings

Cerebral hemorrhage or softening was found in 60% of patients with eclampsia who died within 2 days of the onset of convulsions but in only 20% of those who survived longer. The pathologic findings (in order of decreasing frequency) are cortical petechial hemorrhages, multiple focal softening or petechiae in the white matter or midbrain, hemorrhage into basal ganglia, pia-arachnoid hemorrhage, and hemorrhage in the pons.²¹ A schematic representation of some of these findings is shown in Media file 6. The incidences of subcortical hemorrhage, medium-sized hemorrhages in the outer white matter, and large hemorrhage in the white matter were similar. Microscopically, the brain shows thrombosis of precapillaries and sometimes infarction.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

Considering the significant morbidity and even deaths associated with the condition, aggressive treatment of eclampsia is warranted. Close observation of the blood pressure of pregnant women is very important. Admission to an intensive care unit is justified. Eclampsia also adversely affects the fetus; therefore, when possible, labor should be promptly induced. If fetal lung maturity is a question, expeditious administration of corticosteroid is warranted. If induction and rapid vaginal delivery is not possible, abdominal delivery should be considered. Prevention of any subsequent seizures is another goal. In the past, the choice of anticonvulsant was controversial; however, 2 large multicenter randomized trials have put an end to the controversy—magnesium sulfate is now the drug of choice.²²

• Magnesium sulfate (MgSO₄) is superior to phenytoin sodium and diazepam in controlling recurrent seizures and is associated with lower neonatal morbidity and mortality rates.^{23, 24} Magnesium sulfate should be administered as soon as possible after diagnosis of preeclampsia is confirmed. It should be administered immediately after a seizure, if not administered before. In case of recurrent seizure after magnesium sulfate administration, a bolus of 2 g of additional magnesium sulfate is useful.
• Control of hypertension is very important. If administration of magnesium sulfate does not reduce the blood pressure adequately, other antihypertensive agents should be used. Some of the commonly used agents are hydralazine, labetalol, nifedipine, and sodium nitroprusside.¹ Nifedipine has the advantage of ease of administration via the sublingual route; the other 2 agents can be administered intravenously. In developing countries, a lower cost antihypertensive medication alpha methyldopa is used widely.

Surgical Care

Evaluation for retained products of conception and their removal may be helpful in cases of postpartum eclampsia. In case of antepartum eclampsia, cesarean delivery is useful if immediate vaginal delivery is not feasible.

Consultations

Consulting an ophthalmologist is recommended for evaluation of papilledema or retinal pathology.

Diet

No specific dietary restriction or supplementation is needed for the treatment of eclampsia. With increasing gestational age, serum ionized and total magnesium levels decrease significantly; however, dietary supplementation of magnesium is not known to have any advantages. Several studies evaluating effects of exercise and diet, including aerobic exercise, protein restriction, protein supplementation, increasing or decreasing salt intake, magnesium supplementation, and zinc supplementation, have not produced any clear answers.

For CME/CE activities, see High Fiber in Pregnancy Cuts Risk of Preeclampsia and Eating Chocolate May Decrease Risk for Preeclampsia.

Various trials of supplementation with fish oil or oil of evening primrose, which are rich sources of long-chain fatty acids, have not shown preventative effects consistently. Early studies of dietary calcium supplementation suggest that it may be helpful in preventing toxemia in women who are at highest risk and in women with a low dietary intake of calcium. However, in a large National Institutes of Health trial with healthy nulliparous women randomly assigned at 13-21 weeks’ gestation, calcium supplementation neither reduced the incidence or severity of preeclampsia nor delayed its onset.²⁵ One of the several hypotheses of the pathogenesis of preeclampsia focuses on the oxidative stress caused by the imbalance in prooxidant and antioxidant forces. Preliminary findings on vitamin E and vitamin C supplementation in preeclamptic women are encouraging.²⁶

Activity

Patients with eclampsia are usually monitored in an intensive care setting, so activity is limited. Once they recover from eclampsia, normal activity can be resumed, depending on whether abdominal delivery was performed.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Drug Category: Mineral supplements

Magnesium sulfate is effective in the treatment of eclampsia. It is superior to phenytoin sodium and diazepam in controlling recurrent seizures and is useful for prevention of seizures in women with preeclampsia. Magnesium sulfate also has favorable effects on neonatal mortality and morbidity rates.

Drug Category: Antihypertensives

Aggressive use of antihypertensive medications is necessary if blood pressure remains high after administration of magnesium sulfate. Continued elevation of blood pressure in the setting of eclampsia may cause further cerebral edema or cerebral hemorrhage.

Drug Category: Antiplatelet agents

Toxemia of pregnancy is associated with deficiency of prostaglandins (potent vasodilators) and excess of thromboxane (vasoconstrictor). This leads to the belief that low-dose aspirin with its effects on synthesis of these agents may be useful in preventing toxemia of pregnancy. Antiplatelet agents were associated with a 19% reduction in the risk of preeclampsia when a metaanalysis of 43 trials was performed. This benefit was present in trials where all women or only women at high risk of developing preeclampsia were included.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Deterrence/Prevention

• Proper prenatal care is the important factor in early diagnosis of PIH. This results in adequate supervision and early medical intervention to avoid severe PIH and eclampsia.

Complications

• Cerebral hemorrhage is a serious complication and a frequent finding in fatal cases of eclampsia.
• Stroke is another possible complication, although rare. Vasoconstriction in eclampsia is reversible, but a large-vessel constriction may lead to focal ischemia, resulting in stroke.
• Hepatic rupture is another serious and potentially fatal complication in women with this syndrome.

Prognosis

• Eclampsia may result in significant immediate morbidity and even death; however, most women survive and are free of any long-term sequelae.
• Some women, especially multiparous white women and black women, may have higher long-term incidence of hypertension and related morbidity. This may not be a direct result of eclampsia but may indicate underlying susceptibility for development of hypertension.

Patient Education

• Patient education is important. Discussing warning symptoms of severe PIH and preeclampsia prior to development of severe complications avoids delay in medical intervention.
• For excellent patient education resources, visit eMedicine's Circulatory Problems Center and Pregnancy and Reproduction Center. Also, see eMedicine's patient education article, Seizures Emergencies.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Nonenhanced CT scan of the brain of a woman following an eclamptic seizure showing hypodense areas involving the white matter of occipital lobes and high frontal/parietal lobes.
	View Full Size Image
Media type:  CT

Media file 2:  Axial T2-weighted MRI of the brain of a woman with eclampsia showing abnormal areas (hyperintense lesions) affecting the pons, cerebral peduncles, and internal capsules.
	View Full Size Image
Media type:  MRI

Media file 3:  T2-weighted axial image of the brain in a woman with transient Balint syndrome due to eclampsia showing hyperintense lesions affecting gray and white matter of the occipital and posterior temporal lobes bilaterally.
	View Full Size Image
Media type:  MRI

Media file 4:  Axial T2-weighted images of the brain of a woman with transient cortical blindness and seizure due to eclampsia. Images show abnormal hyperintense areas involving the occipital white matter bilaterally. In addition, a single lesion affecting the white matter of the right frontal lobe is also observed.
	View Full Size Image
Media type:  MRI

Media file 5:  CT scan of head without contrast showing small amount of subarachnoid hemorrhage over the surface of the brain and in Sylvian fissure in two separate patients.
	View Full Size Image
Media type:  CT

Media file 6:  Various histologic features of autopsy findings in the brain of women with eclampsia: (1) pia-arachnoid hemorrhage, (2) medium-sized hemorrhage in outer white matter, (3) subcortical hemorrhages, (4) basal ganglia hemorrhage, (5) multiple focal softening or petechiae, (6) large hemorrhage in white matter, and (7) cortical petechiae (adapted from Sheehan HL, Lynch JB: Cerebral lesions. In: Pathology of Toxemia of Pregnancy. London: Churchill-Livingstone; 1973: 524-53, see text for details).
	View Full Size Image
Media type:  Image

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

1. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. Jul 2000;183(1):S1-S22. [Medline].
2. Shah AK, Nikhar NK, Watson CR. New-onset peripartum seizures - Insight into a common disorder. Neurology. 1998;50 (suppl 4):A253.
3. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. Jun 10 2005;308(5728):1592-4. [Medline].
4. Noris M, Perico N, Remuzzi G. Mechanisms of disease: Pre-eclampsia. Nat Clin Pract Nephrol. Dec 2005;1(2):98-114; quiz 120. [Medline].
5. Conrad KP, Lindheimer MD. Renal and cardiovascular alterations. In: Lindheimer MD, Roberts JM, Cunningham FG, eds. Hypertensive Disorders in Pregnancy. Stamford, CT: Appleton; 1999:263-326.
6. Fitzgerald DJ, Rocki W, Murray R, Mayo G, FitzGerald GA. Thromboxane A2 synthesis in pregnancy-induced hypertension. Lancet. Mar 31 1990;335(8692):751-4. [Medline].
7. Seligman SP, Buyon JP, Clancy RM, Young BK, Abramson SB. The role of nitric oxide in the pathogenesis of preeclampsia. Am J Obstet Gynecol. Oct 1994;171(4):944-8. [Medline].
8. Shah AK, Rajamani K, Whitty JE. Eclampsia: A neurological perspective. J Neurol Sci. Aug 15 2008;271(1-2):158-67. [Medline].
9. Shah AK, Whitty JE. Characteristics of headache in women with eclampsia. Neurology. 1999;52 (suppl 2):A285-86.
10. Shah AK. Non-aneurysmal primary subarachnoid hemorrhage in pregnancy-induced hypertension and eclampsia. Neurology. Jul 8 2003;61(1):117-20. [Medline].
11. Lubarsky SL, Barton JR, Friedman SA, et al. Late postpartum eclampsia revisited. Obstet Gynecol. Apr 1994;83(4):502-5. [Medline].
12. Cunningham FG, Fernandez CO, Hernandez C. Blindness associated with preeclampsia and eclampsia. Am J Obstet Gynecol. Apr 1995;172(4 Pt 1):1291-8. [Medline].
13. Rahman I, Saleemi G, Semple D, Stanga P. Pre-eclampsia resulting in central retinal vein occlusion. Eye. Aug 5 2005;[Medline].
14. Duley L. Pre-eclampsia and the hypertensive disorders of pregnancy. Br Med Bull. 2003;67:161-76. [Medline].
15. Cunningham FG, Fernandez CO, Hernandez C. Blindness associated with preeclampsia and eclampsia. Am J Obstet Gynecol. Apr 1995;172(4 Pt 1):1291-8. [Medline].
16. Hoffmann M, Keiseb J, Moodley J, Corr P. Appropriate neurological evaluation and multimodality magnetic resonance imaging in eclampsia. Acta Neurol Scand. Sep 2002;106(3):159-67. [Medline].
17. Brown CE, Purdy P, Cunningham FG. Head computed tomographic scans in women with eclampsia. Am J Obstet Gynecol. Oct 1988;159(4):915-20. [Medline].
18. Shah AK, Whitty JE. Brain MRI in peripartum seizures: usefulness of combined T2 and diffusion weighted MR imaging. J Neurol Sci. Jul 1 1999;166(2):122-5. [Medline].
19. Sengar AR, Gupta RK, Dhanuka AK, et al. MR imaging, MR angiography, and MR spectroscopy of the brain in eclampsia. AJNR Am J Neuroradiol. Sep 1997;18(8):1485-90. [Medline].
20. Williams K, Galerneau F. Maternal transcranial Doppler in pre-eclampsia and eclampsia. Ultrasound Obstet Gynecol. May 2003;21(5):507-13. [Medline].
21. Sheehan HL, Lynch JB. Cerebral lesions. In: Pathology of Toxemia of Pregnancy. 1973. London, England: Churchill-Livingstone; 524-53.
22. Moodley J, Kalane G. A review of the management of eclampsia: practical issues. Hypertens Pregnancy. 2006;25(2):47-62. [Medline].
23. Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med. Jul 27 1995;333(4):201-5. [Medline].
24. Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet. Jun 10 1995;345(8963):1455-63. [Medline].
25. Levine RJ, Hauth JC, Curet LB, Sibai BM, Catalano PM, Morris CD, et al. Trial of calcium to prevent preeclampsia. N Engl J Med. Jul 10 1997;337(2):69-76. [Medline].
26. Chappell LC, Seed PT, Briley AL, Kelly FJ, Lee R, Hunt BJ, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet. Sep 4 1999;354(9181):810-6. [Medline].

Article Last Updated: Oct 30, 2008