Keywords
preeclampsia, eclampsia, HELLP syndrome, differential diagnosis
Editors’ comment: The fourth edition of Chesley’s Hypertensive Disorders of Pregnancy is a revision of the previous two multi-authored editions. The fact that four editors and an additional 34 co-authors contributed to the current edition is a testament to Leon Chesley’s remarkable single-authored accomplishment published in 1978. This chapter describes the vast clinical spectrum of preeclampsia with the goal of setting the stage for further description by other authors through the eyes of their specific expertise. Emphasized will be knowledge accrued during the 35 years following Chesley’s epic first edition – keeping apace of the information that seems to have increased exponentially in the past three decades. To be sure, the many advances that are chronicled in the chapters that follow stress giant strides in basic research leading to new insights regarding the pathophysiology of preeclampsia, some made with cutting-edge tools in areas such as genetics, immunology, and molecular biology. But before this we thought it important to describe the spectrum of the clinical disease on which the book is focused. Thus, this chapter outlines the vast array of clinical observations that have prompted evidence-based management schemes to improve maternal and perinatal outcomes of the millions of women whose pregnancies are affected by preeclampsia worldwide each year.
Recall that Leon Chesley was a scientist – a PhD who did not practice medicine – but the goals of his studies were always designed with the object to improve pregnancy outcomes as a common denominator. To this end, he espoused the application of scientific observations in the clinic, the hospital, the labor and delivery unit, and importantly, to long-term follow-up of women found to be hypertensive during pregnancy. What follows is a legacy of that keen scientific application of new knowledge to improve the practice of clinical medicine that Dr. Chesley so well communicated in words and deeds.
Introduction
Preeclampsia is much more than hypertension and proteinuria complicating pregnancy – it is a syndrome affecting virtually every organ system. An appreciation of this has been a principal reason for improved clinical management over the past two to three decades. This does not mean, however, that systemic effects were unknown until recently. In the previous chapter we reprinted Chesley’s original and elegant text describing the history of eclampsia from ancient Chinese, Egyptian, Greek, and Indian literature, as well as its management – and mismanagement – through the 20th century. While the anatomical effects of the disorder on brain, kidney, and liver were well described, the focus was placed clinically on convulsions until the end of the 19th century when blood pressure measurement became possible. Also of interest, preeclampsia was termed “toxemia” – it is still utilized by some – because a prevailing thought was that it was caused by circulating poisons. The latter is an obvious reflection in the “purging” era of therapy. Though the term “toxemia” was subsequently downplayed when the designation “preeclampsia” gained preeminence, the following chapters attest that we have returned to an age that focuses on and speculates that circulating proteins such as cytokines, antiangiogenic factors, antioxidants, and other putative compounds activate the endothelium to cause preeclampsia phenotypes. Indeed, some authors now compare the systemic inflammatory state of preeclampsia to that described in the sepsis syndrome.
The concept that preeclampsia is a protean syndrome is important. Like other syndromes, in individual patients, some organ systems are predominantly affected more than others. For example, in some women the primary pathological manifestation may be asymptomatic, albeit dangerously elevated blood pressures of 230/120 mm Hg or higher, while other women may have an eclamptic convulsion with only minimally elevated blood pressure, and with the majority having a clinical picture somewhere in between these. Of cardinal importance is recognition and differentiation of preeclampsia – whether pure or superimposed – from other causes of hypertension because this is the disorder most likely to cause serious maternal and fetal complications. Precise diagnosis, however, may not be possible, in which case, and as underscored throughout the report of the National High Blood Pressure Education Program’s Working Group, and more recently the Task Force of the American College of Obstetricians and Gynecologists on Hypertension in Pregnancy, it is best to manage such women as if they had preeclampsia.
Clinical Manifestations of Preeclampsia Syndrome
Although the cause of the preeclampsia syndrome remains unknown, evidence for its manifestation begins early in pregnancy with covert pathophysiological changes that gain momentum across gestation and eventually become clinically apparent. Unless delivery supervenes, these changes ultimately result in multiorgan involvement with a clinical spectrum ranging from forme fruste manifestations to one of cataclysmic pathophysiological deterioration that is life-threatening for both mother and fetus. As discussed, these are thought to be a consequence of endothelial dysfunction, vasospasm, and ischemia. Whilst the myriad of maternal consequences of the preeclampsia syndrome are usually described in terms of individual organ systems, they frequently are multiple and they overlap clinically.
This chapter is a capsule of the clinical spectrum of this disorder, and some of the subsequent chapters address individual organ system involvement in greater detail. Preeclampsia, characterized by hypertension, proteinuria, edema, and overt or subclinical coagulation and liver involvement, occurs more commonly in nulliparas, usually after 20 weeks gestation, and becomes more common as term approaches. The earlier the onset, the less likely it is to be “pure” preeclampsia, and the higher the probability the disease is superimposed on underlying essential hypertension or a renal disorder. It also has become customary to categorize the disease as “severe,” with the remainder being either “mild” or “nonsevere.” Severe preeclampsia is usually defined by diastolic and systolic levels of>110 and>160 mm Hg, respectively, the appearance of nephrotic-range proteinuria, sudden oliguria, or neurological symptoms such as headache or hyperreflexia, as well as by laboratory tests demonstrating thrombocytopenia and/or hepatocellular disruption. Because a woman with seemingly mild disease – for example, a teenage girl with a blood pressure of 140/90 mm Hg and minimal proteinuria – can suddenly convulse, designations such as mild and severe could be misleading. In fact, de novo hypertension alone in a third-trimester nulliparous woman is sufficient reason to manage as preeclampsia.
Another manifestation of the syndrome is that of early preeclampsia, i.e., that with an onset<34 weeks, and this variant is associated with greater morbidity than late-onset preeclampsia. The possibility that the heterogeneous expression of preeclampsia might indicate subtypes that could have different pathogeneses directing different preventive strategies is important and should be kept in mind as results of clinical trials are evaluated. Nonetheless, at our current stage of knowledge modifying therapy based on such concepts is inappropriate as all preeclampsia is potentially explosive.
The eclamptic convulsion – certainly the most dramatic – and one of the most life-threatening complications of preeclampsia, was once associated with a maternal mortality of 30%. Improved and aggressive obstetrical management has decreased but not eliminated convulsions. Eclampsia is usually preceded by various premonitory signs including headache, visual disturbances, severe epigastric pain, sensation of constriction of the thorax, apprehension, excitability, hyperreflexia, and hemoconcentration. That said, convulsions can still develop suddenly and without warning in a seemingly stable patient with only minimal elevations of blood pressure. It is the capricious nature of this disorder that underlies the need for early hospitalization of women with suspected preeclampsia.
One aspect of the preeclampsia syndrome that is repeatedly discussed throughout this book is that of the HELLP syndrome . This is an acronym for H emolysis, E levated L iver enzymes, and L ow P latelets – and constitutes an emergency requirement for termination of the pregnancy. The syndrome is characterized by hemolysis with marked evidence of both liver and coagulation abnormalities that include serum transaminase and lactic dehydrogenase increasing to>1000 U/L, platelet counts decreasing to<100,000/μL, with schizocytes seen on the blood smear. Although usually fulminant in nature, the HELLP syndrome can be atypical. A deceptively benign form that has an initially mild clinical presentation, with the woman presenting with borderline thrombocytopenia, and perhaps slightly abnormal serum transaminase levels, normal or minimally elevated blood pressure, and little or no renal dysfunction can manifest. But these seemingly mild complications may rapidly become life-threatening when within 24–48 hours there is progression to a more fulminant form.
Finally, there is another uncommon manifestation of atypical preeclampsia that is termed “late postpartum eclampsia,” defined as hypertension and convulsions that develop 48 hours to several weeks after delivery. Some of these women have typical manifestations of preeclampsia and/or eclampsia prodroma. They often present at emergency rooms, where personnel are unfamiliar with gestation-related problems.
Cardiovascular System
Hemodynamic changes normally induced by pregnancy, as well as the severe disturbances of cardiovascular function with preeclampsia or eclampsia, are discussed in detail in Chapter 14 . To summarize, cardiovascular effects can be divided into those that impact myocardial and ventricular functions.
I
Myocardial Function
Serial echocardiographic studies have documented that in preeclampsia there is evidence for ventricular remodeling which is accompanied by diastolic dysfunction in 40% of women. In some of these women, functional differences persisted at 16 months. Ventricular remodeling was judged to be an adaptive response to maintain normal contractility with the increased afterload of preeclampsia. In the otherwise healthy pregnant woman, these changes are usually clinically inconsequential, but if there is underlying concentric hypertrophy, diastolic dysfunction can develop with congestive heart failure and pulmonary edema.
II
Ventricular Function
Despite the relatively high frequency of diastolic dysfunction with preeclampsia, in the majority of women ventricular function is appropriate. Changes are centered on increased cardiac afterload caused by hypertension. At the same time, cardiac filling or preload, whilst substantively affected by normal pregnancy-induced hypervolemia, may be diminished to absent due to preeclampsia, or it may be increased by intravenous crystalloid or oncotic solutions. Importantly, both normally pregnant women, as well as those with severe preeclampsia, have normal ventricular function as shown in Fig. 2.1 and as plotted on the Braunwald ventricular function graph. In both of these groups of women, cardiac output is appropriate for left-sided filling pressures.
Data from studies of preeclamptic women obtained by invasive hemodynamic assessment are confounded because of the heterogeneity of populations and interventions that also may significantly alter these measurements. Ventricular function studies of preeclamptic women from a number of investigations discussed in Chapter 14 are plotted on the graph shown in Fig. 2.2 . Although cardiac function was hyperdynamic in all women, filling pressures were dependent on intravenous fluid infusions. Specifically, aggressive hydration resulted in hyperdynamic ventricular function in most women. As noted, pulmonary edema may develop despite normal ventricular function because of endothelial–epithelial leak that is compounded by decreased oncotic pressure from low serum albumin concentrations. Similar values have been reported using noninvasive whole-body impedance cardiography.
Loss of Pregnancy Hypervolemia
It has been known for over 100 years that hemoconcentration is a hallmark of eclampsia. Zeeman et al. expanded the previous observations of Pritchard et al. that eclamptic women have severe curtailment of normally expected pregnancy-induced hypervolemia ( Fig. 2.3 ). Mechanisms for this are discussed in detail in Chapter 14 . Hemoconcentration is of immense clinical significance. Women of average size should have a blood volume of nearly 4500 mL during the last several weeks of a normal pregnancy, compared with about 3000 mL when they are not pregnant. With eclampsia, however, much or all of the anticipated excess 1500 mL is not available. Clinically, this is of vital importance even when there is average blood loss with cesarean delivery or episiotomy that frequently exceeds 1000 mL In addition, postpartum hemorrhage is more common in women with severe preeclampsia because of factors such as placental abruption, labor induction, and increased risk of operative vaginal or cesarean delivery.
Blood and Coagulation
Hematological abnormalities develop in some women with preeclampsia. Indeed, thrombocytopenia, which was described almost a century ago, can be so severe as to be life-threatening. In addition, the levels of some plasma clotting factors may be decreased, as discussed in detail in Chapter 17 . In some women with severe disease, erythrocytes may display bizarre shapes and undergo rapid hemolysis. The clinical significance of thrombocytopenia, in addition to any impairment in coagulation, is that it reflects the severity of the pathological process. In general, the lower the platelet count is, the greater the maternal and fetal morbidity and mortality. In 1954, Pritchard and colleagues called attention to thrombocytopenia accompanied by intravascular hemolysis in women with eclampsia. As discussed in Chapter 17 , in his first edition of this text, Chesley summarized the available data and concluded that elevated serum hepatic transaminase levels were common in severe forms of preeclampsia and in eclampsia. To call attention to the seriousness of these, Weinstein later referred to this combination of events as the HELLP syndrome , which was described above. This moniker is now used worldwide and we use it throughout this book.
There are also subtle changes consistent with intravascular coagulation, and less often erythrocyte destruction, that commonly accompany preeclampsia and especially eclampsia (see Chapter 17 ). In the first edition of this book, Chesley had already concluded that there was little evidence that these abnormalities are clinically significant. This view was further supported by the results of a large study reported by Pritchard et al., and by the findings of Barron et al. The latter investigators suggested that routine laboratory assessment of coagulation other than platelet count, including prothrombin time, activated partial thromboplastin time, and plasma fibrinogen level, was unnecessary in the management of pregnancy-associated hypertensive disorders. One exception is perhaps when moderate to severe thrombocytopenia – platelet count<100,000/μL – is identified. Others indications are events that coexist and predispose to consumptive coagulopathy. Examples include placental abruption with rapid defibrination, or extensive hepatic necrosis with preeclampsia, or acute fatty liver of pregnancy.
The Kidney
During normal pregnancy, renal blood flow and glomerular filtration rate are increased appreciably. With the preeclampsia syndrome, a number of usually reversible anatomical and pathophysiological changes may occur and are discussed in detail in Chapter 16 . Of clinical importance, renal perfusion and glomerular filtration are reduced. These changes are usually minimal, and a rise in serum creatinine levels to values above those of normal nonpregnant women is infrequent and usually the consequence of very severe preeclampsia or its superimposition on a previous unrecognized kidney disorder. For example, if severe intrarenal vasospasm is profound, thus plasma creatinine may be elevated several times the nonpregnant normal value – up to 2 to 3 mg/dL. As discussed in Chapter 16 , plasma uric acid concentration is typically elevated out of proportion to the reduction in glomerular filtration rate that accompanies preeclampsia.
In most women, urine sodium concentration is often elevated. Levels of urine osmolality, urine:plasma creatinine ratio, and fractional excretion of sodium may suggest that a prerenal mechanism is involved. Clinically, this is important because in severe preeclampsia oliguria may develop despite normal ventricular filling pressures such as shown in Fig. 2.1 . And as shown in Fig. 2.2 , crystalloid infusion increases left ventricular filling pressure, and even though oliguria improves temporarily, this is with a danger of clinically apparent pulmonary edema. Intensive intravenous fluid therapy is not indicated for most women with oliguria.
Proteinuria
At least in the recent past, when protein excretion was detected together with de novo hypertension in late pregnancy, then this combination satisfied the “official” diagnosis of preeclampsia. But with the 2013 Task Force classification, facets other than demonstration of proteinuria are used to make the diagnosis of preeclampsia. These are discussed in Chapter 1 and shown in Table 2.1 . This major change is because proteinuria is not invariably present. First, proteinuria may be a late phenomenon, and some women with preeclampsia may be delivered – or suffer eclamptic convulsions – before it appears. In one example, Sibai noted 10–15% of women with HELLP syndrome do not have proteinuria at discovery. Second, the optimal way of establishing either abnormal levels of urine protein or albumin in pregnant women remains to be defined. Dipstick qualitative determinations depend on the concentration of the urine tested and are notorious for false-positive and -negative results. While a quantitative value of>300 mg/24 h – or its interpolated equivalent in shorter collections – is the standard “consensus” cut-off, this is not irrefutably established. Indeed, Tun et al. proposed a 12-hour collection with a 165-mg upper limit of normal.
| Laboratory Findings | ||||||||
|---|---|---|---|---|---|---|---|---|
| Disorder | Clinical Findings | Hemolysis and Anemia | Bilirubin Elevation | Thrombocytopenia | Creatinine Elevation | AST/ALT Elevation | Intravascular Coagulation | Hypoglycemia |
| Preeclampsia, eclampsia, HELLP syndrome | Variable HTN, HA, proteinuria, convulsions, epigastric pain | Common, usually mild | Usually mild | Mild to moderate | Variable, mild to moderate | Variable, mild to moderate | Rare, mild | No |
| Fatty liver | N&V, mild HTN, impending liver failure | Common, mild to moderate | Common, moderate | Moderate to severe | Common, moderate to severe | Common, moderate | Common, severe (fibrinogen destruction and hypoproduction) | Common, moderate to severe |
| Thrombotic microangiopathy a | Marked hemolysis, thrombocytopenia, CNS findings, occasional HTN, renal involvement | Common, moderate to severe | Variable, mild to moderate | Common, moderate to severe | Variable, mild to moderate | Unusual, mild | Unusual, mild | No |
| Exacerbation SLE b | HTN, proteinuria, lupus flare symptoms, thrombocytopenia | Occasional, mild to moderate | Unusual | Variable, mild to severe | Common, mild to moderate | Unusual, mild | Unusual, mild | No |
a Includes thrombotic thrombocytopenia purpura (TTP) and hemolytic uremic syndrome (HUS).
b SLE=systemic erythematosus. May also have antiphospholipid antibody (APA) syndrome.
Because timed urine specimens can be quite difficult for pregnant women to collect, this has led to recent suggestions that determination of the protein or albumin:creatinine ratio would supplant 24-hour collections. In a systematic review, Papanna et al. concluded that random urine protein:creatinine ratios that are below 130–150 mg/g indicate that the likelihood of proteinuria exceeding 300 mg/day is very low. Midrange ratios, viz. , 300 mg/g have poor sensitivity and specificity and they recommend that a 24-hour specimen be collected for accuracy. Finally, there are several methods used to measure proteinuria, and none detects all of the various proteins normally excreted in urine. In reality, albeit impractical, each hospital laboratory would need to establish its own norms. Finally, there is now available technology that permits the measurement of urinary albumin:creatinine ratios within an outpatient setting.
Also relegated to the past by the 2013 Task Force was the notion that worsening proteinuria indicated worsening preeclampsia. In the new schema, “heavy,” “nephrotic range,” or worsening proteinuria are not necessarily signs of severe disease with ominous indications. Thus, proteinuria has a binary function – either positive or negative, present or absent, or “yes” or “no” – when it is new-onset and is quantified to be 300 mg/day or more in a woman with de novo hypertension. The magnitude of the proteinuria alone as risk marker, in the absence of other ominous signs, has been questioned for decades.
Normally proteins pass the glomerular barrier poorly and filtration of albumin is far greater than that of the other larger globulins. In addition, there are tubular proteins that also enter the urine. The quantity of all urinary proteins is probably below 100 mg/day in most nonpregnant women; however, empirically the upper limit of normal is considered to be>300 mg/day during normal gestation. When the glomerular barrier to proteins is disrupted as it is in many glomerular diseases, preeclampsia included, most of the increased protein in the urine is albumin.
In addition to barrier disruption – the “leak” – the amount of protein in the urine will be determined by the amount of albumin brought to the glomerulus per unit of time, viz. , plasma albumin×renal plasma flow. This is related to the plasma albumin concentration, with less excretion with lower plasma levels for a given leak. Also in the equation is production and catabolism of albumin, all affected by both liver and renal involvement. Thus when considering normal renal physiology and urinary protein excretion, it seems almost inevitable that the magnitude of changes in proteinuria would not make an efficient prognosticator of severity. That said, and given that all confounding variables are not always identifiable, it is prudent to view moderate to heavy proteinuria as both diagnostic of preeclampsia and therefore not to be ignored.
Recovery of Renal Function
In most women, there is minimal renal dysfunction and recovery is the rule. There are, however, some women with very severe forms of preeclampsia who are at risk of varying degrees of acute renal failure. Also designated as acute kidney injury , such degrees of renal failure are usually due to acute tubular necrosis , characterized by oliguria (rarely anuria) and rapidly developing azotemia. Depending on the severity of renal shutdown, the serum creatinine level may increase rapidly, often as much as 1–2 mg/dL daily.
Most often, acute kidney injury is seen in neglected cases, or it is induced in the preeclamptic woman by hypovolemic shock associated with obstetrical hemorrhage, for which adequate blood replacement is not given. Drakeley et al. described 72 women with preeclampsia and renal failure – half had HELLP syndrome and a third had a placental abruption. Looked at another way, Haddad et al. reported that 5% of 183 women with HELLP syndrome developed acute renal failure. Half of these also had a placental abruption, and most had postpartum hemorrhage. Frangieh et al. reported an incidence of 3.8% with eclampsia. In the past, irreversible renal cortical necrosis went on to develop in many of these women, but with moderate resuscitative algorithms this is rare today, and generally seen most often in undeveloped areas of the world.
The Liver
From a clinical standpoint, hepatic involvement usually testifies to the severity of the preeclampsia syndrome. That said, hepatic hemorrhage and cellular necrosis are seldom extensive enough to be clinically relevant. Differentiating characteristics from other obstetrical hepatic disorders are shown in Table 2.1 . As discussed in Chapter 17 , in 1856 Virchow described characteristic lesions commonly found with fatal cases of eclampsia to be regions of periportal hemorrhage in the liver periphery. In their autopsy studies, Sheehan and Lynch reported that some hepatic infarction accompanied hemorrhage in almost half of women with eclampsia. Reports of elevated serum hepatic transaminase levels began to surface in the late 1950s, and over the next 20 years it became appreciated that these changes were also seen with severe preeclampsia and they usually paralleled severity of disease. As discussed, such involvement was termed HELLP syndrome by Weinstein.
From a pragmatic point, liver involvement with preeclampsia may be clinically significant in the following circumstances:
- 1.
Symptomatic involvement, usually manifest by moderate to severe right-upper to midepigastric pain and tenderness, is seen with severe disease. In many cases such women also have elevations in serum hepatic aminotransferase levels – aspartate transferase (AST) or alanine transferase (ALT). In some cases, however, the amount of hepatic tissue involved with infarction may be surprisingly extensive, yet still clinically insignificant. In our experiences, infarction may be made worse by hypotension from obstetrical hemorrhage. Shown in Fig. 2.4 is a CT scan from a woman with severe preeclampsia and massive obstetrical hemorrhage. While there was extensive hepatic infarction visible on the CT scan, there were no clinical symptoms of liver dysfunction.
Figure 2.4
Abdominal CT scan showing subcapsular liver hematoma with areas of decreased attenuation consistent with hepatic infarction.
(From van Lonkhuijzen, with permission.)
- 2.
Asymptomatic elevations of serum hepatic transaminase levels – AST and ALT – are considered markers for severe preeclampsia. Values seldom exceed 500 U/L or so, but can be over 2000 U/L in some women. In general, they inversely follow platelet levels, and they normalize within 3 days following delivery.
- 3.
Hepatic hemorrhage from areas of cellular necrosis and infarction can be identified using CT- or MR-imaging as shown in Fig. 2.4 . Hepatic hemorrhage may form an intrahepatic hematoma or a subcapsular hematoma (see Fig. 17.3 ). These hematomas – especially the subcapsular variety – may rupture with hemorrhage into the peritoneal cavity. It is likely, however, that hemorrhages without rupture are more common than clinically suspected, especially in women with HELLP syndrome. Although once considered a surgical condition, most currently favor observation and conservative management of hematomas unless extensive hemorrhage is ongoing. That said, in some cases, prompt surgical intervention may be life-saving. Rinehart and Vigil De Gracia and their colleagues reviewed over 300 cases and reported that maternal mortality was about 25%. The majority of these hematomas were in women with HELLP syndrome and most were ruptured. In a few cases liver transplant has proved life-saving.
- 4.
Acute fatty liver of pregnancy is sometimes confused with preeclampsia and HELLP syndrome. It too has an onset in late pregnancy, and often there is accompanying hypertension, elevated serum transaminase levels, and thrombocytopenia. It is thought to arise from any of several gene mutations of lipid β-oxidation enzymes that cause accumulation of intracellular fat vesicles causing varying degrees of liver failure. Unlike in women with preeclampsia there is frequently persistent nausea and vomiting, jaundice, and systemic symptoms of 1- to 2-weeks duration. The accompanying coagulopathy from liver failure may be profound, and hemorrhage with operative delivery can be fatal. In most cases, liver function usually improves 2–3 days following delivery.
HELLP Syndrome
As discussed on page 28 and in Chapter 17 , thrombocytopenia is reflective of the severity of the preeclampsia syndrome. As hepatic involvement characterized by elevated serum transaminase levels also became well known as a marker for severity, these two began to be used in combination. As discussed, this constellation of findings is now commonly termed HELLP syndrome. Because there is no strict definition, its incidence varies according to the investigator. In one large study, it was identified in almost 20% of women with severe preeclampsia or eclampsia. In earlier reports, severe morbidity and mortality were described. From a multicenter study, Haddad et al. described 183 women with HELLP syndrome. Adverse outcomes developed in almost 40% of cases, and two women died. Complications included eclampsia (6%), placental abruption (10%), acute renal failure (5%), pulmonary edema (10%), and subcapsular liver hematoma (1.6%). Citing autopsy data, Isler et al. identified associated conditions that included stroke, coagulopathy, acute respiratory distress syndrome, renal failure, and sepsis. Subsequent studies continue to chronicle substantively increased maternal and perinatal morbidity and mortality.
Some clinicians have advocated corticosteroid therapy for amelioration of HELLP syndrome. In a Cochrane Database review, Matchaba and Moodley concluded that there was insufficient evidence that adjunctive steroid use is beneficial. In a later review, Vidaeff and Yeomans reached similar conclusions. At least two recent randomized trials have shown no benefits to corticosteroid therapy in women. These results are discussed in more detail in Chapter 17 , Chapter 20 .
The Brain
Headaches and visual symptoms are common with severe forms of preeclampsia, and associated convulsions define eclampsia. Neuroanatomical and pathophysiological aspects of the brain with preeclampsia syndrome are detailed in Chapter 13 . The earliest anatomical descriptions of brain involvement came from autopsy specimens, but imaging and Doppler studies have added new insights into cerebrovascular involvement. Chapter 13 also discusses the clinical utility of CT scans and MRI, including numerous advances since the previous edition.
Neurological manifestations of the preeclampsia syndrome are several. Each signifies severe involvement and requires immediate attention:
- 1.
Headache and scotomata are thought to arise from cerebrovascular hyperperfusion, which has a predilection for the occipital lobes. According to Sibai, 50–75% of women have headaches and 20–30% have visual changes preceding eclamptic convulsions. The headaches may be mild to severe, intermittent to constant, and, in our experiences, they usually improve after magnesium sulfate infusion is initiated.
- 2.
Convulsions are diagnostic for eclampsia and their proposed pathogenesis is discussed in Chapter 13 .
- 3.
Blindness is rare with preeclampsia alone, but it complicates eclamptic convulsions in 10–15% of women. Blindness has been reported to develop up to a week or more following delivery.
- 4.
Generalized cerebral edema with mental status changes can vary from confusion to coma.
Blindness
As indicated, visual disturbances are common with severe preeclampsia and especially eclampsia. Scotomata are the most common symptoms and these usually abate with magnesium sulfate therapy and/or lowered blood pressure. Visual defects, including blindness, are less common, and usually reversible except in rare cases. They may arise in three potential areas: the visual cortex of the occipital lobe, the lateral geniculate nuclei, and retinal lesions that include ischemia, infarction, and detachments.
Occipital blindness is also called amaurosis – from the Greek “dimming” – and affected women usually have evidence of extensive occipital lobe vasogenic edema on CT scanning and MR imaging. Of 15 such women cared for at Parkland Hospital, blindness lasted from 4 hours to 8 days, but it resolved completely in all cases. Rarely, cerebral infarctions may result in total or partial visual defects ( Fig. 2.5 ). Retinal lesions occasionally complicate the preeclampsia syndrome. These are caused by either retinal ischemia or infarction and are also termed Purtscher retinopathy ( Fig. 2.6 ). Moseman and Shelton described a woman with permanent blindness due to a combination of infarctions in the lateral geniculate nucleus bilaterally as well as retinal infarction. In many cases visual acuity improves, but if caused by retinal artery occlusion, the prognosis is worse. Conditions associated with retinal neovascularization may be more vulnerable to the development of permanent visual defects. In women studied remotely from eclampsia, preliminary observations indicate possible interference with higher-order visual function.
