Late Postpartum Eclampsia with Postpartum Angiopathy: An Uncommon Diagnosis in the Emergency Department

The Journal of Emergency Medicine, Vol. 49, No. 6, pp. e187–e191, 2015 Copyright Ó 2015 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter

http://dx.doi.org/10.1016/j.jemermed.2015.07.019

Clinical Communications: Obstetrics and Gynecology

LATE POSTPARTUM ECLAMPSIA WITH POSTPARTUM ANGIOPATHY: AN UNCOMMON DIAGNOSIS IN THE EMERGENCY DEPARTMENT Deepika Garg, MD,* Brad Rahaman, MD,† Evan G. Stein, MD PHD,‡ and Eitan Dickman, MD, RDMS, FACEP† *Department of Obstetrics and Gynecology, †Department of Emergency Medicine, and ‡Department of Radiology, Maimonides Medical Center, Brooklyn, New York Reprint Address: Deepika Garg, MBBS, Department of Obstetrics and Gynecology, Maimonides Medical Center, 950 49th Street, Apt 3K, Brooklyn, NY 11219

, Abstract—Background: Late postpartum eclampsia is defined as occurrence of eclampsia >48 h after delivery and is a rare clinical entity. The delayed onset and nonspecific symptoms at presentation make this entity a challenge to diagnose in patients presenting to the emergency department (ED); however, early recognition and timely interventions are the keys to reducing morbidity and mortality in patients with late postpartum eclampsia. Case Report: A 28-year-old woman presented to our ED with a chief complaint of headache of 4 days duration, 8 days after an uncomplicated, normal vaginal delivery. Her past medical history was unremarkable and her entire pregnancy was without medical incident. The patient’s examination was within normal limits other than a blood pressure of 152/ 111 mm Hg and pulse of 54 beats/min. Given her undifferentiated headache and the possibility of preeclampsia, the patient was treated with magnesium sulfate, which was subsequently stopped due to worsening bradycardia. Hydralazine was administered for blood pressure control. Three hours after the magnesium was stopped, the patient reported blurry vision, which was immediately followed by a generalized tonic-clonic seizure. After the seizure, lorazepam was given for control of seizures, and the patient was admitted to the medical intensive care unit. The patient was transferred to the postpartum floor 6 days later in stable condition and without any further seizure activity. Why Should an Emergency Physician Be Aware of This?: Patients with late postpartum eclampsia are infrequently encountered in the ED due to the rarity of this condition. Increased awareness of this entity among emergency physicians will

lead to early interventions, which are crucial in decreasing morbidity and mortality in these patients. Ó 2015 Elsevier Inc. , Keywords—headache; seizure

late

postpartum

eclampsia;

INTRODUCTION Eclampsia is defined as a complication of pregnancy after 20 weeks gestation and involves seizure activity superimposed on preeclampsia, which is characterized by elevated blood pressure and one or more of a host of complications that include new-onset proteinuria, low platelets, abnormal liver function tests, renal impairment, pulmonary edema, and neurological or visual symptoms (1). It can present during the antepartum, intrapartum, or postpartum periods. Most patients with postpartum eclampsia present within 24 to 48 h after delivery, whereas late postpartum eclampsia is defined as the occurrence of eclampsia >2 days after delivery. The incidence of eclampsia in developed countries is 1.6–10 cases per 10,000 deliveries, and 11–44% of cases occur in the postpartum period (2,3). Early diagnosis and timely management are crucial steps in reducing the morbidity and mortality associated with this disorder; if left untreated, eclampsia can lead to maternal death due to cerebral edema and seizure activity.

RECEIVED: 29 January 2015; FINAL SUBMISSION RECEIVED: 8 July 2015; ACCEPTED: 25 July 2015 e187

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CASE PRESENTATION A 28-year-old woman, gravid 1 para 1, presented to the ED on postpartum day 8 with complaints of headache for 4 days duration. Four days prior to arrival, she had a visit to the emergency department (ED) of another hospital after the onset of the same headache, at which time she had a normal neurological examination and computed tomography (CT) of the head. At that time, the patient was discharged home with analgesics. Eight days prior to arrival (and 4 days prior to the first ED visit), the patient had vaginally delivered a full-term baby with epidural analgesia after an uncomplicated pregnancy. The patient denied any past medical history or any obstetrical complications, including seizure disorder, migraines, hypertension, and chronic headaches. The headache was described as intermittent, sharp, and was localized to the bilateral frontal and temporal regions with a pain score of 10/10. The headache was exacerbated when supine, and improved in the upright position. She denied any fever, chills, or neck stiffness. The patient’s blood pressure during the pregnancy and the delivery was normal, and at the time of discharge was 90–110/50–70. On physical examination, the patient was in mild distress secondary to the headache. Her initial vital signs in the ED revealed a temperature of 36.6 C (97.8 F), blood pressure of 152/111 mm Hg, pulse of 54 beats/ min, respiratory rate of 18 breaths/min, and oxygen saturation of 100% while breathing ambient air. There was no evidence of head trauma, and the neck was supple. Examination of the heart, lungs, and abdomen were unremarkable. The patient’s neurological examination, including deep tendon reflexes, was normal, as was the fundoscopic examination. Laboratory studies including complete blood count, basic metabolic panel (serum sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, and calcium levels), and liver function tests were all within normal limits. There was no proteinuria. As the patient had an uncomplicated pregnancy with no history of gestational hypertension or preeclampsia in the antepartum, intrapartum, or immediate postpartum periods, and with a reported recent normal head CT scan, venous sinus thrombosis was a diagnostic consideration. Therefore, magnetic resonance venography of the brain was obtained, which showed evidence of intracranial hypotension but no venous sinus thrombosis. The patient was initially started on magnesium sulfate, but this medication was discontinued after 2 h due to bradycardia of 39 beats/min; however, the blood pressure remained at 140/100 mm Hg, for which hydralazine was given. Consultation was obtained from both Obstetrics and Neurology. The patient was evaluated by the Obstetrics

team, which recommended intensive care monitoring of the blood pressure due to possible preeclampsia. The neurologist recommended a magnetic resonance imaging (MRI) study of the brain, valproate for seizure prophylaxis, and intravenous lorazepam as needed for seizure activity, given the bradycardia during magnesium administration. After the consultations were obtained, the patient developed blurry vision followed by a generalized tonic-clonic seizure 3 h after stopping the magnesium. Lorazepam was administered with subsequent resolution of the seizure activity. The patient was admitted to the medical intensive care unit. A CT scan of the head was normal. MRI of the brain showed posterior reversible encephalopathy syndrome (PRES) (Figure 1). A magnetic resonance angiogram of the brain demonstrated evidence of postpartum angiopathy (Figure 2). The patient had no further complications during a 6-day course in the Intensive Care Unit and was transferred to the postpartum unit in stable condition. DISCUSSION Eclampsia occurs in 38–53% of patients during the antepartum, 18–36% of patients in intrapartum, and 11–44% of patients in the postpartum period (3). Postpartum eclamptic seizures usually occur within 48 h of delivery, although they have been reported up to 23 days postpartum (4). It is important to rapidly diagnose late postpartum eclampsia to initiate appropriate interventions and hopefully prevent further complications including coagulopathy, renal failure, pulmonary edema, hepatocellular damage, cerebral ischemia, intracerebral hemorrhage, and even death, in rare cases (3,5). The revised definition of preeclampsia by the American College of Obstetricians and Gynecologists (ACOG) Task Force Report is described in Table 1 (1). Eclampsia is defined as seizure activity in conjunction with preeclampsia. Our patient initially did not meet the criteria of preeclampsia, as she had a normal platelet count, creatinine and transaminase levels, and an absence of proteinuria. As per the most recent ACOG guidelines for the diagnosis of preeclampsia, the presence of hypertension along with neurological symptoms such as headache in a pregnant or recently pregnant patient, even if the patient does not have proteinuria, should raise suspicion for preeclampsia. Other systemic findings have been included in the definition of preeclampsia, as maternal and fetal outcomes cannot be predicted by the degree of proteinuria. Awareness of postpartum preeclampsia has been emphasized, along with minimizing use of nonsteroidal antiinflammatory drugs in patients with elevated blood pressure in the postpartum period.

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Figure 1. Magnetic resonance imaging scan of the brain. Coronal (A) and axial (B) T2-weighted fluid-attenuated inversion recovery imaging shows areas of abnormal hyperintense signal intensity in the cortical and subcortical brain in the bilateral frontal, parietal, and occipital lobes (arrows) in a distribution highly suggestive of posterior reversible encephalopathy syndrome.

Patients with late postpartum eclampsia may not present with the classic symptoms that occur with antepartum and intrapartum eclampsia. Watson et al. reported 132 cases of eclampsia in one center from 1977 to 1982, of which 36 (27%) were in the postpartum group. Seventeen of those patients had late postpartum

Figure 2. Magnetic resonance angiogram (MRA) of the brain. Maximum intensity projection reconstructions of a noncontrast MRA study acquired using three-dimensional time-offlight imaging shows multiple areas of focal narrowing in the left supraclinoid internal carotid artery, the left middle cerebral artery, and the right vertebral artery (arrows) suggestive of reversible cerebral vasoconstrictive syndrome, also known as postpartum angiopathy in this clinical setting.

eclampsia. The most common presentation was headache, which was reported in 82% of cases, followed by visual disturbances in 44% of cases (6). Lubarsky et al. reported 97 (29%) cases of postpartum eclampsia among a total of 334 patients with eclampsia between 1977 and 1992 (7). Out of these 97 cases, 54 (56%) cases occurred more than 48 h after delivery in patients with an established diagnosis of preeclampsia; there was a mean duration of 6 days prior to the development of convulsions. Of the 54 patients with late postpartum eclampsia, 45 patients (83%) presented with the complaint of severe headache prior to the development of seizures (7). Chames et al. reported that among 89 patients with the diagnosis of eclampsia from 1996 to 2001, 29 patients (33%) presented during the postpartum period, and 23 of those occurred more than 48 h after delivery (8). Out of these 23 patients, only 5 (22%) had a diagnosis of preeclampsia at the time of delivery. Headache, again, was the presenting symptom in 87% of these patients. This study further substantiated the predominance of headache as the most common presenting symptom (8). The exact mechanism of seizures in eclampsia is not well defined, but is most likely secondary to a combination of cerebral edema, ischemia, and transitory vasospasm of the cerebral vasculature. The management of eclampsia includes supportive therapy, seizure control, prevention of further seizure activity, and blood pressure control. The mainstay of treatment remains magnesium sulfate therapy, as it stabilizes cellular membrane potential and successfully prevents seizures or recurrent seizures in 95% of cases (9). Benzodiazepines can also be used for seizure control. They can be used as an adjunct

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Table 1. Revised Definition and New Guidelines for the Diagnosis of Preeclampsia by The American College of Obstetricians and Gynecologists (The College) Task Force on Hypertension in Pregnancy on November 2013 As per the American College of Obstetricians and Gynecologists Task Force Report, preeclampsia is defined as: - Systolic blood pressure $140 mm Hg or diastolic blood pressure $90 mm Hg on two occasions at least 4 h apart in a woman with previously normal blood pressure AND - Proteinuria $300 mg in 24 h or protein/creatinine ratio $0.3, or urine dipstick reading of 1+ In the absence of proteinuria, new onset of hypertension with any of the following: - Thrombocytopenia with platelet count of <100,000/mL - Serum creatinine >1.1 mg/dL or doubling of creatinine in the absence of any renal disease - Elevated liver transaminases to twice normal - Pulmonary edema - Cerebral or visual symptoms

or as a second-line medication when there are contraindications to the use of magnesium sulfate, as was seen in our patient after she developed significant bradycardia. Neither diazepam nor phenytoin is as effective as magnesium (10). Labetalol and hydralazine have both been used for blood pressure control in obstetric patients with hypertension; these agents are given when the systolic blood pressure is >160 mm Hg. Labetalol is the preferred agent given its combined alpha and beta blockade, which prevents reflex tachycardia (11). Treatment, however, must be individualized. In our patient who manifested significant bradycardia, the treatment of choice was hydralazine. As per the new ACOG guidelines, oral nifedipine has also been suggested as an equally effective initial antihypertensive. All patients with eclampsia should have an Obstetrics consultation and should be managed in a well-equipped facility with a critical care unit. Posterior reversible encephalopathy syndrome (PRES) is characterized by vasogenic edema in the posterior cerebral circulation. Patients can present with headache, visual disturbances, and seizures. PRES has been noted in association with hypertensive and immunological disorders, as well as in patients with eclampsia (12). It has been postulated that the high blood pressure in eclampsia leads to increased perfusion in the cerebral circulation and vasogenic edema, which can lead to seizures (13). In patients with postpartum angiopathy, a condition also known as reversible cerebral vasoconstrictive syndrome (RCVS), imaging studies demonstrated segmental vasoconstriction of the large or mediumsized cerebral blood vessels, which spontaneously resolves. Rarely, it causes residual neurological deficit or maternal death (14). The etiology of RCVS is not settled but may be related to the same pathophysiology that leads to PRES (15). The incidence of late postpartum eclampsia is increasing due to early hospital discharge after delivery (16). Headache is the most common symptom, but frequent use of epidural anesthesia during delivery can also cause a spinal headache and can cloud the clinical picture. It is therefore important to have a high level of

suspicion when treating postpartum patients to initiate both timely management of blood pressure and seizure prevention. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS CONDITION? Late postpartum eclampsia can manifest with atypical features. The low prevalence of late postpartum eclampsia along with its nonclassical presentation makes this condition challenging to diagnose. Increased awareness and a high degree of suspicion of late postpartum eclampsia amongst emergency physicians can lead to timely identification and early treatment of this entity, which are vital for reducing maternal morbidity and mortality. REFERENCES 1. American College of Obstetricians and Gynecologists (ACOG); Task Force on Hypertension in Pregnancy. Hypertension in pregnancy (Report of the ACOG Task Force on Hypertension in Pregnancy). Obstet Gynecol 2013;122:1122–31. 2. Fong A, Chau CT, Pan D, Ogunyemi DA. Clinical morbidities, trends, and demographics of eclampsia: a population-based study. Am J Obstet Gynecol 2013;209:229.e1–7. 3. Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol 2005;105:402–10. 4. Raps EC, Galetta SL, Broderick M, Atlas SW. Delayed peripartum vasculopathy: cerebral eclampsia revisited. Ann Neurol 1993;33: 222–5. 5. Sibai BM, Spinnato JA, Watson DL, Lewis JA, Anderson GD. Eclampsia. IV. Neurological findings and future outcome. Am J Obstet Gynecol 1985;152:184–92. 6. Watson DL, Sibai BM, Shaver DC, Dacus JV, Anderson GD. Late postpartum eclampsia: an update. South Med J 1983;76(12): 1487–9. 7. Lubarsky SL, Barton JR, Friedman SA, Nasreddine S, Ramadan MK, Sibai BM. Late postpartum eclampsia revisited. Obstet Gynecol 1994;83:502–5. 8. Chames MC, Livingston JC, Ivester TS, Barton JR, Sibai BM. Late postpartum eclampsia: a preventable disease? Am J Obstet Gynecol 2002;186:1174–7. 9. Tso E, Reid RP, Barish RA, Browne BJ. Late postpartum eclampsia. Ann Emerg Med 1987;16:907–9. 10. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995;345:1455–63. 11. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1–22.

Late Postpartum Eclampsia with Postpartum Angiopathy 12. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494–500. 13. Zeeman GG, Hatab M, Twickler DM. Maternal cerebral blood flow changes in pregnancy. Am J Obstet Gynecol 2003;189:968–72. 14. Fugate JE, Ameriso SF, Ortiz G, et al. Variable presentations of postpartum angiopathy. Stroke 2012;43:670–6.

e191 15. Anziska BJ, Dardis C, Levine SR. Reversible cerebral vasoconstriction syndrome: a rose by any other name? Arch Neurol 2011;68: 976–7. 16. Centers for Disease Control and Prevention (CDC). Trends in length of stay for hospital deliveries—United States, 1970–1992. MMWR Morb Mortal Wkly Rep 1995;44:335–7.