Publisher Summary
Postpartum angiopathy (PPA), a cerebral vasculopathy, is considered comparatively rare, but may be under-recognized. The diagnosis is made based on neurologic symptoms in the postpartum setting with documented angiographic findings of multifocal segmental vasoconstriction. Symptoms of PPA are usually encountered in the first 1–2 weeks after an uncomplicated pregnancy and delivery, but can be delayed for up to 6 weeks postpartum. Classically patients present with abrupt, excruciating headaches. The pain is commonly holocephalic and may be accompanied by nausea, visual disturbances, encephalopathy, or seizures. Though there have been cases reported without headache, the absence of this symptom should raise suspicion for other diagnoses, as it is a prominent and early feature in the vast majority of described cases. Headaches can be persistent or may fluctuate and manifest as recurrent thunderclap headaches over several days. Generalized seizures are the second most commonly reported neurologic symptom in PPA, followed by visual disturbances and encephalopathy. A variety of visual disturbances can occur, including transient scotomas, visual field deficit, and cortical blindness.
Postpartum angiopathy (PPA) is a rare cause of stroke in the puerperium. This disorder is grouped with “reversible cerebral vasoconstriction syndromes,” but can result in neurologic deficits or, rarely, death. Clinically PPA is heralded by severe abrupt headaches associated with seizures, visual disturbances, or hemiparesis within 1–2 weeks after a normal pregnancy and delivery. Cerebral angiography demonstrates multifocal segmental vasoconstriction involving the proximal large and medium-sized cerebral arteries, which resolves spontaneously over weeks. Brain imaging can be normal or may demonstrate posterior reversible encephalopathy syndrome (PRES), intraparenchymal hemorrhage, convexal subarachnoid hemorrhage, or ischemic stroke. The underlying pathophysiology remains unknown. Functional vasoconstriction is suspected as a mechanism, rather than a true inflammatory process. There is no established treatment, but calcium channel blockers and magnesium sulfate are often tried. Prognosis is generally favorable, with most patients achieving complete or near-complete recovery within days to weeks. Nevertheless, fatal cases and substantial morbidity are well described.
Background and Context
Acute stroke is a rare but potentially devastating complication during pregnancy or in the puerperium. Whether pregnancy confers an increased risk of stroke compared to age-matched nonpregnant women is not clear and has been studied with conflicting results. A large population-based study in the United States using the Nationwide Inpatient Sample found an estimated threefold increase in stroke incidence in pregnant women , while other studies have found the risk to be as high as 13-fold increase . In contrast, Kittner et al. found an increased risk within 6 weeks after delivery but found no increased risk during pregnancy itself.
The increased risk of stroke in the postpartum period has been a more consistent finding. Traditional cerebrovascular risk factors (e.g., hypertension, smoking, arterial vascular disease, hyperlipidemia) can contribute, but there are additional factors that pertain to the unique physiology of pregnancy. Several factors contribute to a hypercoagulable state in normal pregnancy. Concentrations of von Willebrand factor, factor VIII, and fibrinogen are increased , resistance to protein C develops, and concentrations of protein S are reduced. In addition, platelet aggregation may be increased by higher prolactin concentrations . Postpartum angiopathy (PPA), peripartum cardiomyopathy, eclampsia, dural sinus thrombosis, and intracranial hemorrhage are other potential causes of stroke in this population.
Postpartum Angiopathy
Introduction
PPA, a cerebral vasculopathy, is considered comparatively rare, but may be under-recognized. The diagnosis is made based on neurologic symptoms in the postpartum setting with documented angiographic findings of multifocal segmental vasoconstriction. Our understanding of this condition is largely derived from case reports and small retrospective series, conferring a poor understanding of its true incidence, spectrum, and natural history.
Clinical Features
Symptoms of PPA are usually encountered in the first 1–2 weeks after an uncomplicated pregnancy and delivery, but can be delayed for up to 6 weeks postpartum . Classically patients present with abrupt, excruciating headaches (so-called “thunderclap headaches”). The pain is commonly holocephalic and may be accompanied by nausea, visual disturbances, encephalopathy, or seizures ( Table 4.1 ). Though there have been cases reported without headache , the absence of this symptom should raise suspicion for other diagnoses, as it is a prominent and early feature in the vast majority of described cases. Headaches can be persistent or may fluctuate and manifest as recurrent thunderclap headaches over several days. Generalized seizures are the second most commonly reported neurologic symptom in PPA, followed by visual disturbances and encephalopathy . A variety of visual disturbances can occur, including transient scotomas, visual field deficit, and cortical blindness.
| n (%) | |
|---|---|
| Clinical Symptoms | |
| Headache | 42 (86) |
| Generalized seizures | 28 (57) |
| Focal neurologic deficits | 17 (35) |
| Visual disturbances | 15 (31) |
| Encephalopathy | 14 (29) |
| Radiologic | |
| PRES | 19 (39) |
Intracranial hemorrhage
| 18 (37) 11 (22) 7 (14) |
| Ischemic stroke | 13 (27) |
Focal neurologic deficits (e.g., hemiparesis, sensory loss, aphasia) from ischemic stroke (caused by severe vasoconstriction) or intracranial hemorrhage may develop. In this setting, the patient often will have had several days of headache preceding the onset of hemiparesis, which may initially fluctuate in severity. Because ischemic strokes in PPA often involve the watershed zones between the anterior and middle cerebral arteries, bilateral lower extremity hyperreflexia and/or weakness can be seen.
Hypertension is commonly but not invariably present at initial clinical presentation. In our review of nearly 50 cases in the English literature, nearly half of patients (23/49, 47%) with PPA had a systolic blood pressure <160 mmHg at symptom onset (unpublished data).
Radiologic Findings
Our interpretation of the frequency and severity of radiographic findings seen in PPA is confounded by a selection bias of the patients who undergo brain imaging. Neurologic symptoms late in pregnancy and in the puerperium often prompt a clinical diagnosis of eclampsia (if concomitant hypertension and proteinuria are present) or even “atypical eclampsia” in the absence of those features. Brain imaging is not always performed in these circumstances, and many patients are treated with intravenous magnesium sulfate with resolution of symptoms. If imaging is performed, computed tomography (CT) or magnetic resonance imaging (MRI) may be performed to visualize the brain parenchyma but is often performed without arteriography. Even when vascular imaging is obtained, timing could be an additional factor affecting diagnosis and estimated frequency, as in early PPA initial angiographic studies can be normal with repeat studies showing vasoconstriction . Authors of a recent study of reversible cerebral vasoconstriction syndromes (which only included one patient with PPA) found that vasoconstriction reached a maximum about 2 weeks after onset of headache and often persists longer than symptoms .
Noninvasive techniques such as magnetic resonance angiography (MRA) and computed tomography angiography (CTA) or conventional cerebral angiography are used to evaluate the cerebral vasculature. Multifocal areas of vessel narrowing involving multiple large- and medium-sized arteries are characteristic and should raise suspicion for the diagnosis of PPA ( Figure 4.1 ). Vessel caliber may be dilated or normal between areas of constriction. When dilated, the appearance may be that of “beads on a string.” The anterior cerebral, middle cerebral, distal basilar, and superior cerebellar arteries are most commonly affected . Serial transcranial Doppler (TCD) has also been used to follow blood velocity trends, indirectly assessing the degree of vasoconstriction. Caveats with this approach are that TCD can show normal blood flow velocities in some patients , and elevated velocities may reflect hyperemia rather than vasoconstriction.
Brain MRI or head CT findings vary and can demonstrate evidence of ischemic stroke, reversible vasogenic edema, or acute intracranial hemorrhage. Imaging may be initially normal (up to 35% of cases), but most of the time subsequent imaging reveals an abnormality. Posterior reversible encephalopathy syndrome (PRES) is the most commonly identified abnormality, seen in 40% (unpublished data) to 54% of cases . Intracranial hemorrhage, often lobar intraparenchymal or small convexal subarachnoid hemorrhage occurs in nearly 40% and ischemic stroke in nearly 30% ( Table 4.1 ).
Differential Diagnosis
Other potentially life-threatening disorders can present in the postpartum setting similar to thunderclap headaches and should be excluded ( Table 4.2 ). Aneurysmal subarachnoid hemorrhage, cerebral venous sinus thrombosis, arterial dissection, and pituitary apoplexy must be included in the differential diagnosis. Brain imaging and in most cases, cerebrospinal fluid (CSF) examination for xanthochromia, cell count, total protein, and glucose should be done. Angiography can exclude ruptured cerebral aneurysms, dissection, or cerebral venous thrombosis.
