Cerebrovascular pathology, pregnancy and post-partum

Cerebrovascular pathologies are rare during the peripartum period but account for 4 to 11% of peripartum maternal deaths. They occur predominantly in the third trimester of pregnancy and in the first few weeks postpartum.

These pathologies are not specific to the peripartum period, and although various physiological changes are classically mentioned, the literature does not conclusively indicate a significantly increased incidence. Nevertheless, due to their morbidity and mortality, both gynecologists and their teams must be able to recognize and manage them promptly.

Pathophysiological Aspects

Several physiological factors specific to pregnancy are implicated in favoring cerebrovascular events:

• Hematological Factors - Hypercoagulable State
  • Increased coagulation factor activity + decreased fibrinolytic activity
  • Peaks during the third trimester and normalizes a few weeks postpartum
• Hormonal Factors
  • Role of estrogens in vasodilation, potentially favoring vascular malformations?
• Hemodynamic Factors
  • Gradual increase in cardiac output during pregnancy (up to 50% at term)
  • Decreased vascular resistance and blood pressure, normalizing at the end of pregnancy
  • During labor:
    • Each contraction increases cardiac output by 20% + transfer of 250 to 300 cc of blood from the uterine to the systemic circulation → increased cerebral blood flow, blood pressure, and central venous pressure
    • Valsalva maneuvers → peaks in blood pressure and intracranial pressure
  • Blood loss during delivery → decreased cerebral blood flow (favors venous thromboses)
  • Histological changes in arteries (medial thickening, fiber fragmentation, muscle hyperplasia)

Epidemiology

In addition to the usual cardiovascular risk factors, the following should be considered: advanced maternal age, thrombophilia, black ethnicity, and obstetric complications (infection, hemorrhage).

Cerebrovascular complications account for 4 to 11% of peripartum maternal deaths. The most common are cerebral hemorrhages, cerebral venous thromboses (CVT), and complications secondary to eclampsia.

However, literature data do not allow for a conclusion of a significantly increased relative risk of different types of stroke during pregnancy, possibly due to recruitment biases.

General Considerations for Management During Pregnancy and Postpartum

Management should be discussed among gynecologists, intensivists or internists, and neurologists. In general:

• Avoid acetylsalicylic acid (ASA) during the 1^st trimester (teratogenicity of low doses?). Reduced doses of 60-80 mg for the rest of the pregnancy if necessary (risk of patent ductus arteriosus closure abnormalities).
• If anticoagulation is indicated, two possible regimens (teratogenicity of vitamin K antagonists [VKA]):
  • Simplest: heparins with VKA switch 1 week postpartum
  • Heparins during the first trimester → VKA from the 13^th to 36^th week of gestational age (WGA) → heparins → VKA 1 week postpartum
  • For cerebral venous thromboses, anticoagulation should last for a total of at least 6 months, with a minimum of 6 weeks postpartum.
• No oral contraception after delivery in case of ischemic stroke
• Insufficient data regarding thrombolysis risks during pregnancy…
• For cerebral venous thrombosis: prophylactic LMWH during subsequent pregnancies
• Not codified, but consensus on prophylactic LMWH during subsequent pregnancies in case of AT III deficiency
• If indicated, no particular contraindication for neurosurgery or endovascular treatments, but perform an emergency cesarean if the fetus is sufficiently mature + fetal distress or major maternal risk or obstetric reasons
• Avoid controlled hypotension and mannitol during pregnancy
• Do not forget that in case of eclampsia, the first "treatment" is delivery or pregnancy termination. Always discuss.
• If stereotactic radiotherapy has been performed for an arteriovenous malformation (AVM) → wait at least 2 years before a new pregnancy.

20 to 25% of the etiological workups of cerebrovascular events occurring during pregnancy or postpartum yield negative results. In addition to the usual causes, certain etiologies are specifically or more frequently found in these patients:

Arterial Ischemic Strokes

Eclampsia

• Rare in Western countries (2/1000 pregnancies) but one of the leading causes of maternal mortality.
• Classic clinical presentation: headaches + visual disturbances (< retinal or occipital involvement) + altered consciousness + seizures
  • 2-12% → HELLP syndrome
• Severe forms → similar to hypertensive encephalopathy
  • MRI T2 sequences, proton density, FLAIR: confluent subcortical hyperintense areas (+- brainstem or cerebellum). Diffusion shows hyperintensities associated with increased water diffusion coefficient. +- petechial hemorrhages on gradient echo. +- hemorrhagic areas.
• MRA: possible focal segmental vasoconstriction zones
• Clinical-radiological course is usually favorable, but sequelae are possible.

Acute Postpartum Cerebral Spastic Angiopathy

A rare but classic clinical-radiological syndrome. The initial clinical picture is usually severe (sometimes mimicking a subarachnoid hemorrhage: severe headaches, vomiting, seizures +- regressive focal deficits) but generally has a benign course. Risk factors: administration of oxytocics or bromocriptine.

MRA shows multiple intracerebral arterial narrowings (! sometimes only positive after a few days) that disappear on follow-up after a few weeks. Edematous areas or cerebral infarctions may also be observed.

There is no evidence of specific management. Consider blood pressure control similar to that of hypertensive encephalopathy or ischemic stroke, and administration of nimodipine (6 x 60 mg/day PO) to prevent vasospasm extension. Endovascular therapeutic indications to relieve vasospasms are not established.

Spastic cerebral angiopathies are not specific to the postpartum period (drug users - ++ amphetamines and cocaine, ergot derivatives and antimigraine drugs, secondary to eclampsia, sympathomimetic intoxication, etc.).

Sheehan's Syndrome = Pituitary Apoplexy

It corresponds to ischemic necrosis of the pituitary due to hemodynamic failure. It is not specific to pregnancy but is favored by possible postpartum hemorrhage as well as increased pituitary volume and vascularization during pregnancy. Typical clinical presentation: pallor, asthenia, lack of lactation +- headaches and visual disturbances. Diagnosis is based on CT scan or MRI. Management is mainly supportive + management of endocrine disorders.

Choriocarcinoma

Choriocarcinoma is a trophoblastic tumor affecting 1 in 40,000 pregnancies → brain metastases in 1 in 5 cases. Possible damage to the vascular walls leading to ischemia, sometimes months before the tumor syndrome appears.

Arrhythmias

Although data are scarce, it is commonly accepted that pregnancy may decompensate underlying cardiac arrhythmias (++ atrial fibrillation), potentially leading to cardioembolic strokes.

Amniotic Fluid Embolism

Amniotic fluid embolism occurs during abortion or vaginal delivery. ++ older women, multiparas, prolonged labor, vaginal or cervical tear.

Classic clinical presentation: sudden dyspnea, cyanosis, shock, seizures due to severe hypoxia +- focal deficits. Rare brain lesions due to paradoxical cerebral embolism.

Symptomatic management in the ICU.

Peripartum Cardiomyopathy

Accounts for < 1% of pregnancy-related cardiac complications. ≈ 1/3000 pregnancies in Western countries. ++ during the last month of pregnancy and postpartum.

It typically presents as dilated heart failure. Possible presentation as cerebral embolism. Frequent systemic and pulmonary emboli. Mortality is high and recurrences are common in subsequent pregnancies.

Treatment: management of heart failure. Systematic anticoagulation if arrhythmias, unexplained syncope, or thromboembolic events are present. Prophylactic anticoagulation is controversial, to be discussed on a case-by-case basis with cardiologists.

Cerebral Venous Thromboses

Despite insufficient data, it is commonly accepted that the frequency of cerebral venous thromboses (CVT) increases in the postpartum period (debated during pregnancy). Peak frequency 10 to 20 days postpartum. Nevertheless, systematically perform a thrombophilia workup. Note: rare gestational toxemia cases with disseminated intravascular coagulation (DIC).

• Classic clinical presentation: severe headaches (sudden onset and in bursts), +- vomiting, epileptic seizures, focal deficits, + non-fluctuating or progressive consciousness disorders.
• Risk factors: known thrombophilia, dehydration (++ hyperemesis gravidarum and postpartum), uterine infection, amniocentesis, cesarean, and preeclampsia.
• If suspicion: MRI FLAIR + T2 + diffusion + 3D TOF (excludes arterial infarction) + T1 with fat saturation (hematoma).
• MRA: sensitivity 60 to 90%, in the best-case scenario, by indirect signs only.
• Contraindications: CT angio (or MRI) of the dural sinuses.
• Perform MRI + MRA of the cerebral veins in the absence of another cause of stroke. If confirmed, prolonged anticoagulation (LMWH 3 to 6 months) + anticoagulation for at least 6 weeks postpartum.

Hemorrhagic Strokes

Despite the lack of significant data, a generally increased risk is commonly accepted.

Intraparenchymal Hemorrhages

Main predisposing factors include:

• Eclampsia → multiple petechial hemorrhages, mostly (sub)cortical, or more rarely, actual hematomas. Poor prognosis (maternal mortality ≈ 40%, fetal mortality ≈ 30%).
• Cerebral metastasis of a choriocarcinoma
• Pre-existing risk factors : Moya-Moya disease, chronic hypertension, vasculitis, coagulation disorders, substance abuse

There is no particular demonstrated risk of rupture of arteriovenous malformations or cavernomas... expert opinions on this matter are divided.

Subarachnoid Hemorrhages

No evidence of an increased incidence... expert opinions are divided.

Etiological Workup

Despite pregnancy-specific risk factors, any cerebrovascular event requires the same etiological workup as it would in a young patient outside of pregnancy. Refer to the corresponding chapters.

Regarding complementary examinations, avoid CT scans and prefer MRI (avoid gadolinium if possible during pregnancy). There are no absolute contraindications to pre-partum angiography if the number of fluoroscopic images is limited (note: look for and treat possible transient fetal thyroid dysfunction at birth if necessary) and standard precautions are followed. There is no contraindication to performing transesophageal echocardiography.

The Case of Pregnant Women (or Women Planning Pregnancy) with Asymptomatic Intracranial Vascular Malformations

The incidental discovery of an unruptured intracranial vascular malformation in a pregnant woman or one planning pregnancy is a common source of concern for patients and gynecologists.

Whether it is an arteriovenous malformation, an aneurysm, or a fistula, there is no evidence of an increased risk of rupture during pregnancy, nor is there any specific approach recommended for these patients. They should be treated (or not) based on standard considerations. It is only advisable to ensure closer clinical and blood pressure monitoring.

Bibliography

Bradley WG et al., Neurology in clinical practice, 5th ed., Butterworth-Heinemann, e-dition, 2007

EMC, traité de neurologie, Elsevier, 2018