Neurocritical Care Complications of Pregnancy and Puerperum

Journal of Critical Care 29 (2014) 10691081
Contents lists available at ScienceDirect
Journal of Critical Care

journal homepage: www.jccjournal.org
Neurocritical care complications of pregnancy and puerperum

Jennifer A. Frontera, MD a,, Wamda Ahmed, MD b
a
b
Cerebrovascular Center of the Neurological Institute, Cleveland Clinic, Cleveland, Ohio

Neuroscience Intensive Care Unit, Departments of Neurology, Emory, Atlanta, Georgia
a r t i c l e
i n f o
Keywords:
Pregnancy
Puerperum
Neurologic complications
Review
a b s t r a c t
Neurocritical care complications of pregnancy and puerperum such as preeclampsia/eclampsia, hemolysis,
elevated liver enzymes, low platelets syndrome, thrombotic thrombocytopenic purpura, seizures, ischemic
and hemorrhagic stroke, postpartum angiopathy, cerebral sinus thrombosis, amniotic uid emboli,
choriocarcinoma, and acute fatty liver of pregnancy are rare but can be devastating. These conditions can
present a challenge to physicians because pregnancy is a unique physiologic state, most therapeutic options
available in the intensive care unit were not studied in pregnant patients, and in many situations, physicians
need to deliver care to both the mother and the fetus, simultaneously. Timely recognition and management of
critical neurologic complications of pregnancy/puerperum can be life saving for both the mother and fetus.
2014 Elsevier Inc. All rights reserved.
1. Introduction
Intensive care unit admission during pregnancy is a rare
occurrence, accounting only for approximately 0.1% to 1.3% of all
pregnancies [13]. However, neurologic complications in pregnancy
can be life threatening. An overview of neurologic complications of
pregnancy can be found in Table 1. Early identication of neurologic
dysfunction and prompt evidence-based neurocritical management
can signicantly reduce the morbidity and mortality associated with
these disorders.
2. General critical care considerations

Although most critical care is administered to pregnant patients in a
similar fashion to the nonpregnant patient, some circumstances merit
discussion. First, airway changes occur during pregnancy, primarily
related to weight gain but also oropharyngeal diameter narrowing that
may be a consequence of uid retention as well as the growth of nasal
polyps that can occur during pregnancy [4,5]. These factors can all lead
to worsening Mallampati scores and intubation difculty. In addition,
pregnant patients are more prone to reux and aspiration of gastric
contents during intubation and develop hypoxemia more quickly after
periods of apnea due to increased metabolic oxygen demands. Rapid
sequence intubation is routinely used during pregnancy due to
increased aspiration risk, and cricoid pressure should be applied to
further mitigate against aspiration. Advanced options for intubation in a
patient with an anticipated difcult airway include awake beroptic
intubation, laryngeal mask airway, and video laryngoscopy.
Corresponding author. Cleveland Clinic Foundation, Cerebrovascular Center, 9500
Euclid Ave S80, Cleveland, OH 44195. Tel.: +1 216 445 3248; fax: +1 216 636 2061.
E-mail address: frontej@ccf.org (J.A. Frontera).
http://dx.doi.org/10.1016/j.jcrc.2014.07.010
0883-9441/ 2014 Elsevier Inc. All rights reserved.
Second, in mechanically ventilated pregnant patients, the target

PaCO2 should be between 30 to 32 mm Hg to replicate normal
respiratory alkalosis that occurs during pregnancy (pH target
7.40-7.47). However, extremely low PaCO2 (b30 mm Hg) can lead to
uterine blood ow restriction and should be avoided, whereas
maternal hypercapnia can lead to fetal respiratory acidosis.
Third, careful attention should be given to sedatives administered
to the pregnant patient. Lorazepam has teratogenic effects, and its use
should be limited to patients with acute seizure. Nonsteroidal
antinammatory drugs cause premature closure of the ductus
arteriosus and should be avoided late in pregnancy. Opioids are
generally considered safe in pregnancy, and propofol is listed as
pregnancy category B, although reports of its use are limited.
Fourth, vasopressors for hemodynamic support can constrict
uterine blood ow. First-line management of symptomatic hypotension in pregnancy should include volume resuscitation and the left
lateral decubitus position to improve venous return. In patients with
active hemorrhage, transfusion should be considered. In those who
are refractory to these rst-line therapies, norepinephrine is a
reasonable vasopressor choice. Ephedrine has been associated with
lower fetal pH values and should generally be avoided [6].
Finally, fetal heart rate and uterine monitoring should be
considered in critically ill pregnant patients in addition to routine
intensive care unit monitoring.
3. Diagnostic considerations
The choice of brain imaging studies in pregnancy should account
for the diagnostic benets for the mother and radiation exposure risks
for the fetus. According to the American Congress of Obstetricians and
Gynecologists (ACOG), growth restriction, mental retardation, and
microcephaly are the most common of effects of high-dose radiation
[7]. The fetus is at greatest risk for radiation between 8 to 15 weeks;
1070
J.A. Frontera, W. Ahmed / Journal of Critical Care 29 (2014) 10691081
however, this risk is not found with radiation exposure less than 5 rad
[8]. Fetal radiation exposure with computed tomography (CT) head is
less than 1 rad. When a head CT is needed, maternal counseling should
take place when possible, and an abdominal shield should be placed
for extra protection. American College of Radiology guidelines also
agree that less than 5 rad is not likely to cause fetal harm at any
gestational age.
Radiopaque contrast agents that may be used with CT contain
derivatives of iodine, and studies have shown conicting results
regarding possible harmful effects on fetal thyroid function [9,10]. The
ACOG guidelines recommend avoiding radiopaque contrast, unless it
is essential for diagnosis [8]. Nonradiopaque contrasts such as iohexol,
iopamidol, iothalamate, ioversol, ioxaglate, and metrizamide have
been studied in animals without evidence of harm to the fetus.
Magnetic resonance imaging (MRI) and ultrasonography are not
associated with known adverse fetal effects and are considered safe in
any trimester. Magnetic resonance imaging safety is documented in
1.5T scanners, but little is known regarding the safety of 3T or higher
tesla scanners. Paramagnetic contrast used with MRI (gadolinium)
was studied in animal models and showed an increased risk of
spontaneous abortion, skeletal, and visceral abnormalities at 2 to 7
times the recommended human dose and should be used only when
the benet exceeds the potential risk.
Catheter angiography/digital subtraction angiography can expose
the fetus to substantial radiation and should be used with caution. It is,
however, the criterion standard for diagnosing cerebral aneurysms,
arteriovenous malformations (AVMs), and postpartum angiopathy.
Fetal monitoring should be considered in all pregnant patients and
may include fetal heart rate monitoring and obstetrical ultrasound
noting fetal biophysical prole, fetal weight, position, placental
position and blood ow, and amniotic uid volume.
4. Preclampsia/eclampsia
4.1. Epidemiology
Preeclampsia/eclampsia is a common condition occurring in 7.5%
of pregnancies worldwide and accounting for 10% to 15% of maternal
deaths [11]. The pathophysiology of preeclampsia/eclampsia is
thought to be due, in part, to placental underperfusion and hypoxia,
which leads to the release of antiangiogenic factors (soluble fms-like
tyrosine kinase 1 and soluble endoglin). These factors impair maternal
endothelial function leading to increased vascular permeability,
vasoconstriction, activation of the coagulation cascade, and microangiopathic hemolysis [12]. Preeclampsia/eclampsia has been associated
with neurologic complications such as seizure, reversible encephalopathy, ischemic stroke, intracerebral hemorrhage (ICH), and HELLP
syndrome as well as medical complications including myocardial
infarction, pulmonary edema, acute renal failure, thrombocytopenia,
disseminated intravascular coagulopathy (DIC), placental abruption
with massive hemorrhage, and liver hematoma or rupture.[13] The
usual onset of preeclampsia or eclampsia is by the 20th week of
gestation; however, symptoms can also begin in the postpartum
period (typically within 48 hours to 4 weeks of delivery). Preeclampsia is dened as hypertension more than 140/90 and proteinuria more
than 300 mg per day and is typically accompanied by peripheral
edema. If the patient also experiences seizures, this state is dened as
eclampsia (Table 2). Of mildly preeclamptic women, 1 in 400
progresses to eclampsia, whereas 1 in 50 with severe preeclampsia
develops seizures [14].
Abnormal development of the placenta leading to poor placenta
perfusion, ischemia, endothelial dysfunction, and activation of
platelets has been linked to preeclampsia and intrauterine growth
abnormalities [15]. General risk factors for pregnancy-induced
hypertension include chronic hypertension, age more than 40 or
less than 18 years, family history of preeclampsia, history of
preeclampsia, rst pregnancy, chronic renal disease, inherited

thrombophilia (especially antiphospholipid disease), connective
tissue disease, diabetes, multiple fetal gestation, obesity, black race,
hydrops fetalis, fetal growth restriction, partner-related factors, and
hydatidiform mole. The most important predisposing risk factor for
preeclampsia is chronic hypertension. Indeed, roughly 25% of women
with chronic hypertension go on to develop preeclampsia [13].
Women who have a history of preeclampsia have an increased risk for
stroke and hypertension decades after the diagnosis of preeclampsia.
Preeclampsia affords 1.5 to 2 times the risk of cerebrovascular disease
and stroke, even after adjusting for other stroke risk factors [1619].
Women with early preeclampsia (before 32-week gestation) fare
even worse, with a 5-fold risk of stroke compared with later onset
preeclampsia [13].
One of the most common serious neurologic complications of
preeclampsia/eclampsia is posterior reversible encephalopathy syndrome (PRES). This reversible encephalopathy typically occurs in the
setting of hypertension and presents with headache, visual impairment (blurred vision and scotoma related to elevated intracranial
pressure (ICP) or cortical blindness related to posterior circulation
edema), and/or generalized tonic-clonic seizures. This syndrome may
be related to a failure of autoregulation at the levels of the capillaries
in the watershed zones, with the posterior zones being the most
vulnerable, possibly because of reduced sympathetic innervation of
the vertebrobasilar vasculature [20,21]. In theory, cerebral hyperperfusion related to loss of autoregulation and blood-brain barrier
breakdown leads to uid and protein accumulation in tissue with
resulting edema and microhemorrhage [22,23].
4.2. Diagnosis
The diagnostic criteria for preeclampsia and eclampsia are listed in
Table 2. In the context of PRES, MRI imaging typically reveals posterior
circulation territory nonenhancing, increased uid attenuated inversion recovery (FLAIR)/T2 signal, signifying vasogenic edema. Diffusion
weighted imaging/apparent diffusion coefcient sequence sequences
are usually negative. Magnetic resonance (MR) venography should be
considered to rule out cerebral venous thrombosis (CVT), which may
have similar FLAIR/T2 signal change and present in a similar clinical
fashion to PRES, with symptoms of elevated intracranial pressure
including headache, nausea, vomiting, and blurred vision. Because the
treatment of CVT is quite different from the treatment of preeclampsia/eclampsia, this distinction should be made urgently (see discussion of CVT below). Preeclampsia and eclampsia have also been
associated with true ischemic stroke, likely related to hypertension. In
circumstances of true ischemia, a full stroke evaluation including
transthoracic and transesophageal echocardiography and imaging of
the extracranial and intracranial cerebral circulation should be
undertaken as outlined below. Eclampsia is characterized by generalized tonic-clonic seizures that may occur in the absence of the above
MRI ndings.
4.3. Treatment
The ACOG recommends management for systolic blood pressure
(BP) at least 160 mm Hg and/or diastolic BP at least 110 lasting for at
least 15 minutes [14]. Labetolol is considered rst-line treatment, and
hydralazine is a widely used alternative. The degree of systolic
hypertension or the rate of increase of mean arterial pressure from
baseline levels may be the most important predictor of cerebral injury
and infarction. In extremely hypertensive patients (180/120 mm Hg),
a target diastolic BP of 100 to 105 mm Hg should be achieved within 2 to
6 hours. Long-term antihypertensives for use in pregnancy include
methyldopa, labetolol, nifedipine, and hydralazine. -blockers that lack
blockade (eg, atenolol) have been linked to lower placental and fetal
weight [24,25]. Angiotensin-converting enzyme inhibitors, angiotensin
receptor blockers, and direct renin inhibitors are contraindicated in

pregnancy, as they have been associated with fetal, cardiac, and renal
abnormalities [26]. Nitroprusside use can lead to fetal cyanide toxicity if
used for more than 4 hours. For breast feeding mothers, the American
Academy of Pediatrics rates the following as allowed: propranolol,
metoprolol, labetalol, diltiazem, nifedipine, nicardipine, verapamil,
captopril, enalapril, and diuretics.
Magnesium sulfate is the treatment of choice for eclampsia-related
seizures (see Table 4). Roughly 10% of eclamptic patients will have
recurrent seizures if not treated. The Eclampsia Trial Collaborative
Group conducted 2 randomized trials. In the rst, patients were
randomized to receive either magnesium or diazepam and in the
second, either magnesium or phenytoin. Those receiving magnesium
had 50% fewer seizures compared with diazepam (13% vs 28%
recurrence, respectively) and 33% fewer seizures compared with
phenytoin (6% vs 17%, respectively). There was less acute respiratory
failure and pneumonia in the magnesium compared with phenytoin
group, although there were no differences in maternal or fetal mortality
or outcome [27]. Magnesium sulfate is contraindicated in pregnant
myasthenic patients because it can precipitate myasthenic crisis.
In general, delivery of the placenta is curative for preeclampsia/
eclampsia and results in complete symptom resolution within
48 hours to 4 weeks postpartum.
4.4. Prevention
In a large meta-analysis of 46 trials and 32891 women, low-dose
aspirin has been shown to be benecial in preventing preeclampsia,
gestational hypertension, and preterm birth when started earlier
than 16 weeks gestation, in patients at risk for preeclampsia/eclampsia
[15,2830]. Chest and American Heart Association guidelines recommend
low-dose aspirin, starting from the second trimester (12th week) for
women at high risk for preeclampsia (age N35 years, preexisting
hypertension, diabetes, renal disease, obesity, or a history of preeclampsia/eclampsia) [13,31]. Calcium supplementation (1 g/d) has also been
shown to reduce the rate of pregnancy-related hypertension and
preeclampsia and is recommended by the American Heart Association
for women with low dietary calcium intake [13,32].
1071
100 000 cells/L, total bilirubin at least 1.2 mg/dL, and aspartate
aminotransferase at least 70 IU/L. [34] Noncontrast head CT may
reveal intracranial hemorrhage including intraparenchymal hemorrhage, subdural hematoma, or SAH.
5.3. Treatment
Delivery of the fetus after maternal stabilization is curative and
should be performed in the presence of DIC, multiorgan dysfunction,
liver infarction, liver hemorrhage, pulmonary edema, renal failure,
placental abruption, nonreassuring fetal status, or at least 34-week
gestation. In stable cases less than or equal to 34-week gestation,
corticosteroids may be delivered to assist in fetal lung development,
but delivery should not be delayed more than 48 hours. Platelet
transfusion can be considered for active bleeding or before delivery
for thrombocytopenia less than or equal to 20 000 cells/L. In patients
with intracranial hemorrhage, it is recommended that platelets be
maintained at least 50 000 cells/L. Steroids do not improve maternal
outcome [35,36].
5.4. Prognosis
With prompt delivery, the prognosis is generally favorable. Most
patients begin to recover within 48 hours of delivery, and mortality
rates have been reported at 1% [37]. The recurrence rate in subsequent
pregnancies is low.
6. Thrombotic thrombocytopenic purpura and hemolytic
uremic syndrome
6.1. Epidemiology
Thrombotic thrombocytopenic purpura and hemolytic uremic
syndrome (TTP-HUS) is rare (1 in 25 000 pregnancies) [38] but
associated with high mortality. In some case series of TTP-HUS, 10% to
25% of patients were pregnant or in the puerperal period [39,40]. Like
eclampsia, TTP-HUS occurs around 20th week of gestation through
the postpartum period. However, unlike eclampsia, hypertension in
the context of TTP-HUS is not severe.
4.5. Prognosis
6.2. Diagnosis
The 2 most common causes of peripartum mortality accounting for
60% of deaths are pregnancy-related hypertension and venous
thromboembolism. Preeclampsia/eclampsia is associated with 10%
to 15% of maternal deaths worldwide [33] but less than 1% of deaths in
developed nations. The recurrence rate for eclampsia is approximately
2% in subsequent pregnancies.
5. Hemolysis, elevated liver enzymes, and low platelets
5.1. Epidemiology
Hemolysis, elevated liver enzymes, and low platelets occurs in 0.1% to
0.8% of pregnancies and in 10% to 20% of women with severe
preeclampsia/eclampsia. It typically presents between 28- to 36-week
gestation with nausea, vomiting, abdominal pain, hypertension, and
proteinuria (in 85%) [34]. Complications include DIC, placental abruption, pulmonary edema, acute renal failure, liver hematoma, and retinal
detachment. Intracranial hemorrhage due to low platelets is a feared
complication. Minor trauma may lead to subdural hematoma, subarachnoid hemorrhage (SAH), or contusions/intraparenchymal hemorrhage.
5.2. Diagnosis
Characteristic laboratory ndings include microangiopathic hemolytic anemia with schistocytes, platelet count less than or equal to
Thrombotic thrombocytopenic purpura and hemolytic uremic

syndrome has a classic pentad of microangiopathic hemolytic anemia,
thrombocytopenia, neurologic abnormalities (including altered mental status, coma, seizure, ischemic stroke, ICH, headache, and
reversible posterior leukoencephalopathy syndrome), renal abnormalities, and fever without other etiology. The presence of the full
pentad is rare, and the diagnosis of TTP only requires the presence of
thrombocytopenia and microangiopathic hemolytic anemia, without
any other clear etiology. Laboratory studies reveal evidence of
hemolytic anemia with increased lactate dehydrogenase, increased
indirect bilirubin, reduced or absent haptoglobin, schistocytes and
helmet cells on peripheral blood smear, and increased reticulocytes.
Coagulation studies (activated partial thromboplastin time, prothrombin time, international normalized ratio (INR), brinogen, brin
degradation products, and direct Coombs test) are typically normal. In
TTP, ADAMTS13 (von Willebrand factor-cleaving protease) becomes
depleted through activation of an autoantibody leading to accumulation of large von Willebrand factor multimers, platelet activation,
and deposition of platelet-rich thrombi throughout the body. An
ADAMTS13 level less than 10% represents severe deciency and
conrms the diagnosis of TTP. Although activity between 10% to 50% is
low, these levels can occur in hospitalized patients with inammatory
disorders. Pregnancy is known to trigger episodes of congenital or
acquired severe ADAMTS13 deciency.
1072
Table 1
Overview of neurologic complications of pregnancy
Complication
Neurophysiologic Seizure
Neuropathy
Risk Factors
Condition
Incidence
Severe preeclampsia
Localization-related epilepsy
Seizures in the month before pregnancy
AED polytherapy
Pregnancy-related uid retention
Preeclampsia/eclampsia
History of epilepsy
CVT
Ischemic or hemorrhagic stroke
Carpal tunnel syndrome
Eclampsia occurs in 1/1000 deliveries [92]
Increased lumbar lordosis
Meralgia paresthetica (lateral

femoral cutaneous neuropathy)
Femoral neuropathy
Preeclampsia (Bell palsy)
Neuromuscular junction
disease
Cerebrovascular
Fetal macrosomia
Fetal malpresentation
Prolonged lithotomy position
Prolonged second stage of labor
Improper use of stirrups or retractors
Preexisting myasthenia gravis
Ischemic stroke
Transplacental passage of IgG

antiacetylcholine receptor antibodies can
lead to neonatal myasthenia gravis
(10%-20% of infants born to myasthenic
mothers)
Pregnancy-induced hypertension
ICH
Cesarean delivery
Postpartum infection
Peripartum cardiomyopathy
Gestational trophoblastic disease
Gestational diabetes
Hypercoagulable state of pregnancy
Pregnancy-induced hypertension
SAH
Obdurator neuropathy
Bell palsy
Myasthenia gravis
Postpartum exacerbations occur in 30% of

myasthenics
rst trimester and acute postpartum
period are highest risk [95]
(most common)
CVT (venous infarcts)
Postpartum cerebral angiopathy
Amniotic uid emboli
Trophoblastic embolism
Air embolism
Relative risk 0.7 during pregnancy (not

different from general population) and 8.7
postpartum (6 wk from delivery) [96]
compared with the general population
(most common)
Advanced maternal age
HELLP syndrome
Black race
TTP-HUS
Smoking
CVT
Coagulopathy [60]
AVM
Hemorrhagic conversion of an
ischemic stroke
Pituitary apoplexy
Bleeding metastases from
choriocarcinoma
Postpartum angiopathy may be related to Aneurysm rupture
preeclampsia or eclampsia
AVM
Immunologic
Movement
disorders
Oncologic
Multiple sclerosis
Hyperkinetic
CNS tumors
Assisted reproductive technology
History of frequent MS relapses before

pregnancy
Breastfeeding may be related to reduced
postpartum relapses (conicting data)
Acute rheumatic fever
(chorea gravidarum)
Antiphospholipid syndrome
(chorea gravidarum)
Anemia (restless legs syndrome)
Hormonal changes can accelerate growth
of meningiomas and vestibular
schwanommas
Fluid retention can increase tumorrelated edema
Increased intraabdominal pressure due to

enlarging uterus exceeds CSF drainage
pressure leading to hydrocephalus/
elevated ICP
Carpal tunnel occurs in 2%-35% of

pregnancies [93]
2-4 increased risk of Bell palsy during
pregnancy
Neuropathies are most common during
the third trimester [94]
Immune-mediated demyelination
Chorea gravidarum
Restless legs syndrome
Metastases from choriocarcinoma
The following tumors may enlarge

during pregnancy
Meningioma
Pituitary tumors (prolactinomas)
Vestibular schwannomas
Relative risk 2.5 during pregnancy and

28.3 postpartum [96]
No increased risk of SAH (due to

aneurysm or AVM) during pregnancy or
the postpartum period [57]
However, the risk of aneurysm rupture is
highest during the third trimester [58]
Among women with known AVM,
rupture rate 3.5% per year during
pregnancy vs 3.1% per year among
age-matched nonpregnant women
(no difference) [59]
Pregnancy reduces the risk of MS
activity, but postpartum period
increases the risk [97]
Pregnancy does not affect the type,
severity, or long-term disability of MS
Occurs during the second-fth month of

pregnancy
Symptoms resolve within weeks to
months spontaneously [98]
Up to 20% of patients with
choriocarcinoma have brain metastases
at the time of diagnosis [99]
1073
Table 1 (continued)
Complication
Other
Risk Factors
Condition
Incidence
Shunt malfunction occurs in 25%-50% of
pregnancies
Most common in third trimester [100]
Ventriculo-peritoneal
shunt malfunction
Abbreviations: CNS, central nervous system; IgG, immunoglobulin G; MS, multiple sclerosis.
The differential diagnosis for TTP in pregnancy includes postpartum acute renal failure and preeclampsia/eclampsia with superimposed DIC, both of which are more common than TTP. These
entities can be distinguished by coagulation studies, which reveal low
brinogen, prolonged activated partial thromboplastin time and
prothrombin time, and elevated brin degradation products in the
context of DIC. In contrast, TTP involves platelet consumption and
activation without activation of the coagulation cascade.
6.3. Treatment
Plasma exchange should be initiated immediately, when the
diagnosis of TTP is clinically suspected. Plasma exchange removes
autoantibodies to ADAMTS13 and large von Willebrand factor multimers. Infusion of plasma repletes ADAMTS13 levels. Serum
ADAMTS13 levels can be sent before the initiation of plasma
exchange, but plasma exchange should not be withheld while waiting
for results. In the case of extremely low ADAMTS13 levels (b10%), the
addition of corticosteroid or rituximab treatment can be considered.
Platelet transfusion has anecdotally been associated with worsening
neurologic symptoms, although this has not borne out in studies [41].
Platelet transfusion can be considered for bleeding or platelets less
than or equal to 20 000 cells/L or less than or equal to 50 000 cells/L
in the context of intracranial hemorrhage. In severe cases, where TTP
cannot be readily distinguished from preeclampsia or HELLP syndrome, and the fetus is viable, delivery should be induced. However,
delivery does not cause resolution of TTP-HUS. There have been no
reports of transmission of TTP to the fetus, although placental
infarction can occur and lead to intrauterine fetal demise.
6.4. Prevention
Women with a history of TTP should be followed up closely in
subsequent pregnancies for the development of symptoms suggestive
of TTP. Serial complete blood count and platelet studies are
recommended for early detection. Prophylactic plasma exchange,

however, is not recommended in the absence of symptoms or
laboratory evidence of TTP because risks may outweigh benets [42].
6.5. Prognosis
Untreated mortality rates for TTP in pregnancy approach 90% [43],
whereas plasma exchange reduces mortality rates to 25% [44,45].
Recurrent TTP-HUS has been described during subsequent pregnancies in several case series [38,39].
7. Seizures and epilepsy
7.2. Epidemiology
Although 90% of women with epilepsy have a normal pregnancy,
epilepsy remains the most common cause of seizure in pregnancy.
Five percent of women with epilepsy experience a seizure during
labor or delivery [46]. Risks for seizure in pregnancy include
localization-related epilepsy, seizures in the month before pregnancy
and antiepileptic drug (AED) polytherapy. Antiepileptic drug levels
are also affected by pregnancy due to uid shifts leading to seizure
breakthrough or status epilepticus (SE). Seizure freedom for at least 9
months before pregnancy is associated with an 84% to 92% chance of
remaining seizure free during pregnancy [47].
7.3. Diagnosis
Evaluation of seizure in pregnancy is similar to a standard work-up
and should include brain imaging in patients with rst-time seizure or
a change in seizure semiology (preferably with MRI), electroencephalogram, and baseline blood work including toxicology studies and
AED levels, if applicable. It is important to note that free AED levels are
more accurate than total levels due to increased plasma protein
binding in pregnancy. Free levels are readily available for AEDs that
Table 2
Diagnosis of preeclampsia and eclampsia [14]
Mild preeclampsia
Severe preeclampsia
(Both of the following met)
(Mild preeclampsia plus one or more of the following)
(All below criteria met)
New onset elevated BP on at least 2 separate

measurements at least 6 h, but no more
than 7 d apart
Systolic BP 140 mm Hg or
Diastolic BP 90 mm Hg
CNS dysfunction:
Preeclampsia criteria met
Proteinuria 0.3 g in a 24-h urine specimen
Severe headache
Altered mental status
Visual abnormality (blurred vision, scotoma, cortical blindness)
Symptoms of liver capsule distention:
Right upper quadrant or epigastric pain
Nausea/vomiting
Extremely elevated BP on at least 2 measurements 6 h apart
Systolic BP 160 mm Hg
Diastolic BP 110 mm Hg
Transaminitis N2 upper limit of normal
Platelets b100 000 per L
Proteinuria 5 g in a 24-h urine specimen
Oliguria b500 mL in 24 h
Fetal growth restriction
Pulmonary edema or cyanosis
Eclampsia
New onset generalized tonic-clonic seizures
Absence of other neurologic conditions that

could account for seizure
1074
Table 3
Differential diagnosis for seizure in pregnancy
Disease
Incidence and mortality
Most common cause
Period
Potential neurologic complications
Preeclampsia/
eclampsia
1.6-10 cases per 10 000 deliveries in

developed countries [101]
7.5% of pregnancies and 10%-15% of
maternal deaths worldwide [11]
Rare, often fatal if not treated
promptly with plasma exchange
Similar frequency to prepregnancy
with consistent AED treatment and
drug level monitoring
Placental underperfusion and hypoxia

leading to release of antiangiogenic
factors (soluble fms-like tyrosine kinase
1, soluble endoglin) [12]
ADAMTS13 deciency does not account
for all cases in pregnancy
Absent or subtherapeutic AED levels
Week 20 of gestation to
postpartum period
Seizures, ICH, ischemic stroke, PRES,

elevated ICP, HELLP syndrome
20th week of gestation up to

the postpartum period
Risk of seizure is unchanged
from rst to third trimester in
N50% [46]
Seizure during labor or
delivery occurs in 5% of
women with epilepsy [46]
Most common in postpartum
period (6 weeks from
delivery) [96] but can occur
throughout pregnancy
Throughout pregnancy
Seizure, headaches, encephalopathy, ICH,

ischemic stroke, PRES [102]
SE in b2%
TTP-HUS
Epilepsy
Higher risk in localization-related

epilepsy
Stroke
34.2 per 100000, with mortality rates
(Either ischemic
ranging from 4.1% to 14.7% [54]
or hemorrhagic)
Cerebral venous
thrombus
11.4 per 100 000 deliveries
Amniotic uid
emboli
Rare, although catastrophic and

considered the second most common
cause of maternal death in US
Systemic
hemorrhage
17% of maternal death [105].
Ischemic: preeclampsia/eclampsia,
cerebral venous thrombus, and AFE
Hemorrhagic: preeclampsia/eclampsia,
AVM, or aneurysm [104]
Pregnancy-related hypercoaguable state,
preexisting hypercoagulapathy,
dehydration
Amniotic uid enters maternal
circulation
Uterine atony, placental abruption, or

abnormal placenta
Fetal hypoxia and congenital anomalies

[103]
Focal neurologic decits, seizures,
herniation
Ischemic or hemorrhagic stroke, seizures,

elevated intracranial pressure
Typically during delivery or

Embolic ischemic stroke, seizure,
in the immediate postpartum hypoxic-ischemic encephalopathy after
period
catastrophic cardiopulmonary collapse
(watershed ischemia) [86]
During delivery or
CNS ischemia due to hypoperfusion and
postpartum
hypoxic-ischemic injury leading to
seizure
Abbreviation: US, United States.
bind to protein including phenytoin, valproic acid, carbamezapime,

and phenobarbital. It is reasonable to follow total AED levels in
medications that have less protein binding such as leviteracetam and
lamotrigine. Special consideration should be given to pregnancyassociated conditions that can cause seizures as listed in Table 3.
7.4. Treatment
The management of seizures and SE is similar to that in
nonpregnant patients (Table 4). It is important to obtain an adequate
history and to rule out eclampsia before treating, as seizure
management strategies differ for epileptics and eclamptics. During a
seizure, the patient should be placed in the left lateral decubitus
position, to maintain uterine blood ow and prevent aspiration [48].
Oxygen via face mask is recommended to avoid hypoxia that can
occur with hypoventilation interictally or in the postictal period.
During seizures, fetal bradycardia lasting 3 to 5 minutes can occur and
is followed by compensatory tachycardia and loss of heart rate
variability. Nonreassuring fetal heart tracings for over 10 to
15 minutes despite maternal resuscitation with anticonvulsants, BP
control, and oxygen may indicate placental abruption and/or the need
for emergent delivery. In noneclamptics, rst-line therapy for seizures
in pregnancy should include lorazepam (up to 0.1 mg/kg intravenous
[IV]) followed by a loading dose of either fosphenytoin or leviteracetam. Indeed, leviteracetam monotherapy appears to confer a low
risk of major congenital malformations [49]. Maintenance therapy
with either leviteracetam or the patients baseline AED is reasonable.
In eclamptics, treatment with magnesium sulfate is the standard of
care (Table 4). Status epilepticus is diagnosed in any patient with
seizures (either clinical and/or electrographic) continuing for more
than 5 minutes, and refractory SE is diagnosed in patients who are
refractory to an initial benzodiazepine and a second AED [50]. In such
patients, intubation is usually required. For eclamptics, immediate
delivery of the fetus is indicated once maternal stabilization has
occurred. For noneclamptics with SE, an anesthetic infusion (either
midazolam or propofol) is the preferred third-line agent. Many
practitioners favor midazolam infusion (0.2-2 mg/kg per hour titrated
to seizure suppression or burst suppression) over propofol due to

risks of propofol infusion syndrome, characterized by refractory lactic
acidosis and renal failure. All patients with SE should undergo
continuous electroencephalogram monitoring. Because benzodiazepines, phenobarbital, and primidone can remain in neonatal plasma
for several days, care should be taken to monitor infants for sedation
or drug withdrawal after delivery [51].
7.5. Prevention
Many pregnant women stop taking AEDs during pregnancy due to
misinformation. However, AEDs should be continued throughout
pregnancy, unless the patient has been seizure free for a protracted
period of time ( 2 years). If the decision is made to taper AEDs, this is
ideally done 6 months before pregnancy.
In general, the AED that is most effective at controlling a womans
epilepsy should be continued throughout pregnancy. The overall rate
of congenital malformations related to AED exposure in utero is 4% to
6% [52]. Fetal malformations have been most strongly linked to
valproic acid (neural tube defects in 1%-2%, meningomyelocele,
cardiovascular, and urogenital malformations). Because of these
data, valproic acid should be avoided during pregnancy. Other drugs
have also been linked to higher rates of congenital malformations
including phenytoin (cardiac malformations, cleft palate, genitourinary defects, and neuroblastoma), carbamazepine (spina bida),
phenobarbital (cardiac malformations, cleft palate, and genitourinary
defects), benzodiazepines, and topiramate (cleft lip/palate). Lamotrigine monotherapy after the rst trimester is not associated with an
increased risk of congenital malformations; however, use during the
rst trimester may increase the risk of cleft lip/palate, and higher
doses may increase malformation risks throughout pregnancy.
Leviteracetam, oxcarbazepine, and gabapentin appear to have a low
congenital malformation risk when used as monotherapy, according
to some registries. Additional risk factors for fetal malformations
include AED polytherapy, low folate levels, a family history of birth
defects, and low maternal education level. Use of folic acid
1075
Table 4
Treatment of pregnancy-related neurologic emergencies
Condition
Treatment
Hypertensive emergencies, preeclampia, eclampsia
Stabilization and delivery of the fetus/placenta in the case of preeclampsia/eclampsia
Steroids do not improve maternal outcome [35,36]
HELLP
TTP-HUS
Seizure
Ischemic stroke
ICH or SAH
Postpartum angiopathy
CVT
AFE
First line: labetalol or hydralazine IV push

Second line: continuous infusion of labetalol or nicardipine
Long-term BP control: methyldopa, labetolol, nifedipine, hydralazine
Avoid ACEI, ARB, direct renin inhibitors, nitroprusside
Delivery is curative and the only effective treatment
Transfuse platelets for signicant maternal bleeding or for platelet count 20 000 cells/L
For intracranial hemorrhage, maintain platelet count 50 000 cells/L particularly if neurosurgical
intervention is indicated
Plasma exchange and fresh frozen plasma infusion
Platelet transfusion for bleeding or platelet 20 000 cells/L or 50 000 cells/L (if intracranial
hemorrhage, particularly if neurosurgical intervention planned)
Corticosteroids or rituximab can be used in severe cases
In epileptics: continuation of home medication is reasonable
Avoid use of valproate particularly during the rst trimester
Avoidance of phenytoin, carbamezapine, and phenobarbital during pregnancy may reduce the risk of
cleft palate (phenytoin, carbamezapine) and cardiac malformations (phenobarbital) (12)
AED monotherapy is preferred to polytherapy during the rst trimester [47]
Eclampsia: magnesium sulfate with IV loading dose of 4-6 g in 100 mL of uid over 15-20 minutes
followed by continuous infusion of 1-3 g/h until 24 h after delivery
Serum magnesium level of 4.8-8.4 mg/dL is considered to be the therapeutic range [48]
BP control, glucose control, use of statins, aspirin within 48 h, and surgical options are similar to those
of the general population
Secondary stroke prevention with anticoagulation should be considered for patients with atrial
brillation, cardiac thrombus, thrombophilia-associated stroke, paradoxic emboli-associated with
DVT, prosthetic heart valves, and in some cases of extracranial carotid or vertebral artery dissection.
During pregnancy, low molecular weight heparin is the preferred means of anticoagulation [31].
Warfarin may be safely used in the postpartum period, even during lactation
BP management similar to other hypertensive emergencies in pregnancy
Full doses of low molecular weight heparin during pregnancy and low molecular weight heparin or
vitamin K antagonist postpartum are recommended [13]
Patients with CVT should be anticoagulated even in the presence of ICH
Epilepsy: lorezepam 2-4 mg IV (maximum dose 0.1 mg/kg), load with fosphenytoin (20 mg/kg IV)
using prepregnancy body weight or AED patient is taking at baseline
In eclamptics: magnesium sulfate (see below)
In nonepileptics and noneclamptics: leviteracetam monotherapy appears to confer a low risk of major
congenital malformations [49]
Limiting the dose of lamotrigine or valproic acid in the rst trimester reduces the risk of congenital
malformations (12)
To reduce the risk of poor cognitive outcome in the fetus, polytherapy, valproic acid, phenytoin, and
phenobarbital should be avoided (12)
While using magnesium infusion, monitor for hyporeexia, hypoventilation, and hypotension
Deliver the fetus and placenta in the case of preeclampsia/eclampsia
IV tPA is relatively contraindicated in pregnancy but may be used after risk/benet discussion
Intraarterial tPA and mechanical thrombolysis may be options, although angiography is associated
with substantial radiation exposure for the fetus
Reversal of coagulopathy
Securing ruptured aneurysm or AVM before delivery if possible with abdominal shielding during angiogram
Calcium channel blocker for headache and reducing vasoconstriction
Steroid trial, especially if vasculitis is suspected
Induced hypertension with IV vasopressors can be considered
Full anticoagulation for a duration of at least 6 months and must continue for at least 6 weeks
postpartum in CVT [106]
There is no specic treatment for AFE, and management is primarily supportive

Early stabilization from shock, including uids and pressor support
Achieve goal of PaO2 N65 mm Hg
Nitric oxide can be considered for pulmonary hypertension.
Extracorporeal membrane oxygenation can be considered.
Cryoprecipitate may assist in the removal of amniotic uid debris from the blood [86]
Early neonatal delivery is recommended and improves neonatal outcome
Abbreviations: ACEI,angiotensin converting enzyme inhibitors; ARB, angiotension receptor blocker; DVT, deep vein thrombosis.
1076
supplementation during pregnancy may reduce AED-associated

malformations [53].
Phenobarbital, primidone, phenytoin, carbamazepine, valproate,
levetiracetam, gabapentin, lamotrigine, oxcabazepine, and topiramate
all cross the placenta. Primidone, levetiracetam, gabapentin, lamotrigine, and topiramate all transfer into breast milk to a greater extent
than valproate, phenobarbital, phenytoin, and carbamezapine [53].
Lamotrigine, because it crosses into breast milk at a higher rate than
other AEDs and sedating drugs (phenobarbital and primidone) should
probably be avoided in breastfeeding mothers.
7.6. Prognosis
Having a seizure during pregnancy likely increases the risk of
maternal or fetal injury. Indeed, fetal bradycardia and decelerations
have been recorded during both generalized tonic-clonic seizures and
complex partial seizures [52]. Placental abruption and miscarriage
due to maternal trauma during a seizure also present risks to the
mother and fetus.
8. Stroke
8.1. Epidemiology
The overall incidence of ischemic or hemorrhagic stroke during
pregnancy/puerperum is 34.2 per 100 000 deliveries [54], which
exceeds that of nonpregnant women (21 per 100 000 [55]). The
postpartum period ( 6 weeks from delivery) is the highest risk
period for both ischemic and hemorrhagic strokes. Indeed, an
increased risk of thrombotic events including stroke, myocardial
infarction, and venous thromboembolism persists for up to 12 weeks
postpartum [56]. Roughly 10% of strokes occur antepartum, 40% occur
during delivery, and 50% occur in the postpartum period [54]. There is
no overall increased risk of SAH (due to aneurysm or AVM) during
pregnancy or the postpartum period [57]. However, the risk of
aneurysm rupture is highest during the third trimester [58]. Among
women with known AVM, the rupture rate is 3.5% per year during
pregnancy vs 3.1% per year among age-matched nonpregnant women
(nonsignicant difference) [59].
Risk factors for ischemic stroke, ICH, and SAH in pregnancy are
outlined in Table 1. The largest risk factor for both ischemic and
hemorrhagic stroke is pregnancy-related hypertension [6062]. Other
risk factors for stroke include maternal age (N35 years), arterial
disease, heart disease, smoking, hyperlipidemia, thrombophilia, sickle
cell disease, substance abuse, infection, migraine with aura, and black
race [54]. The risk of stroke in pregnancy doubles in blacks and those
more than age 35 years [54]. Less common risk factors include HELLP
syndrome, TTP-HUS, hypercoagulable state of pregnancy (activated
protein C resistance, low protein S levels, and increased brinogen)
[13], trophoblastic embolism, amniotic uid embolism (AFE), air
embolism, postpartum cerebral angiopathy, and pituitary apoplexy.
Peripartum dilated cardiomyopathy is rare and occurs during the last
month of gestation through the rst 5 months postpartum and
predisposes patients to cardioembolic ischemic stroke. It is more
common in black, older, and multiparous women.
8.2. Diagnosis
The standard stroke evaluation should begin with brain imaging.
Because MRI is safe in pregnancy, it is the imaging study of choice.
Typical MRI noncontrast sequences used in acute stroke evaluation
include diffusion weighted imaging, apparent diffusion coefcient
sequence, FLAIR, T1, T2, and gradient echo sequences. However, in
patients with acute stroke or who are eligible for thrombolysis or those
with suspected ICH or SAH, MRI may present a considerable delay, and a
noncontrast head CT may be preferable to evaluate risks and benets of
acute stroke treatment. Intracranial and extracranial vessel imaging can

be performed with time of ight MR angiography or carotid Doppler and
transcranial Doppler to identify vessel stenosis/occlusion. Magnetic
resonance imaging and magnetic resonance angiography of the neck with
fat saturation may be useful if dissection is suspected. Catheter
angiography (digital subtraction angiography) can expose the fetus to
substantial radiation and should be used with caution. However, it is the
criterion standard for diagnosing cerebral aneurysms, AVMs, and
postpartum angiopathy. Computed tomography angiography is often
used in nonpregnant patients to evaluate for large-vessel occlusions or
vascular malformations; however, both the radiation exposure and
radiopaque contrast side effects (which include nephrotoxic effects and
harmful effect to fetal thyroid development) make CT angiography a
suboptimal study for pregnant patients (see diagnostic considerations
section).
Transthoracic and/or transesophageal echocardiography can detect
cardiac sources of stroke such as left atrial appendage thrombi, dilated
cardiomyopathy, aortic arch atherosclerosis, endocarditis, or patent
foramen ovale with associated paradoxical embolus. When a patent
foramen ovale is detected, an evaluation for deep vein thrombosis in the
lower extremities and pelvic veins should be undertaken, using either
ultrasound or MRI/MR venogram. A thrombophilia evaluation can be
considered in patients with ischemic stroke and consists of blood testing
for factor V Leiden, prothrombin gene mutation, antithrombin III level,
protein C and S activity and level, antiphospholipid antibodies (lupus
anticoagulant and anticardiolipin antibodies), 2 glycoprotein, homocysteine, methylenetetrahydrofolate reductase, and lipoprotein a.
8.3. Treatment
8.3.1. Ischemic stroke
The management of stroke in pregnancy should follow a similar
strategy to that of the general population. According to the American
Heart Association, pregnancy is a relative, not absolute contraindication to intravenous recombinant tissue plasminogen activator (IV tPA)
for acute ischemic stroke, when there are no other contraindications
[63]. There are no large trials examining the safety and efcacy of
tissue plasminogen activator (tPA) in pregnancy; however, IV tPA
given during pregnancy was rarely associated with fetal or maternal
adverse effects in a case series of 372 patients [64]. Tissue
plasminogen activator does not cross the placenta, and case reports
demonstrate that tPA-related complications are similar to those noted
in large trials of nonpregnant patients. Therefore tPA, which is known
to improve outcomes in ischemic stroke, should be strongly
considered when indicated during pregnancy, and risks and benets
should be discussed with the patient and/or legally authorized
representative [65]. In general, IV tPA is indicated within 3 hours of
symptom onset in most patients and within 4.5 hours in select
patients less than age 80 years, with an NIH stroke scale less than 25
and without a history of anticoagulant use or diabetes-associated
stroke. Intraarterial thrombolysis or mechanical clot retraction can be
considered in patients with contraindications to IV tPA or in those
with large-vessel strokes who do not improve after IV tPA. Acute BP
management, use of statins, early aspirin therapy, glucose control, and
surgical options are similar to those used in the general population.
8.3.2. ICH and SAH
The most common causes of hemorrhagic stroke are ruptured AVM,
cerebral aneurysm, and eclampsia [66]. Because many ICHs are related
to preeclampsia/eclampsia, treatment of BP and emergent delivery of
the fetus should proceed as outlined above. Ruptured intracranial
aneurysms should be treated as they would be in the general
population, with the exception that nimodipine, which is used to
prevent delayed cerebral ischemia in patients with SAH, has been
linked to fetal teratogenicity and should be avoided [67]. Endovascular
coiling is less invasive and generally preferred to clipping, [6870]
although it comes with greater radiation exposure. Surgical repair,

conversely, comes with an additional anesthesia risk compared with
endovascular repair. Endovascular and surgical approaches to ruptured
AVM repair should be similar to those in the general population.
Unruptured, asymptomatic aneurysms, and asymptomatic AVMs can be
observed during pregnancy, and patients can attempt vaginal delivery
[71]. Patients with unsecured, ruptured aneurysms or ruptured,
untreated arteriovernous malformations may be considered for cesarean section, although it appears that maternal and fetal mortality rates
are similar with instrumented vaginal delivery or cesarean delivery.
Patients with coagulopathy-associated ICH should undergo reversal of such agents emergently. Although the risk of spontaneous ICH
increases with platelet counts below 10 000/mm3[7274], there are
little data evaluating the risk of ICH expansion or recurrent ICH in
patients with thrombocytopenia. It is therefore difcult to prescribe a
platelet count below which patients with ICH should receive a platelet
transfusion, although in practice, many caregivers will transfuse
platelets for levels less than or equal to 50 000 cell/L, particularly if
there is a planned neurosurgical intervention.
In patients with suspected or measured elevation of ICP, rst-line
therapy should include elevation of the head of the bed 30 to 45,
maintaining the head in midline position to promote jugular venous
outow, sedation to eliminate pain or agitation, fever control,
and treatment of hypercapnia. In patients with a mass lesion or
hydrocephalus, neurosurgery should be consulted for ventriculostomy
and/or mass evacuation. In those with persistently elevated ICP or
suspected elevated ICP, osmotic therapy is indicated. Of note, drugs
typically used in the context of elevated ICP may have deleterious effects
on the fetus. For example, mannitol, used for treatment of elevated ICP,
has been associated with fetal hypoxia and acid-base disturbances. A
reasonable alternative to mannitol for the management of elevated ICP
is hypertonic saline. Options for dosing include bolus dosing of 23.4%
saline (over 15 minutes via a central line), bolus dosing of 2% or 3% saline,
and continuous infusion of 2% or 3% saline (typically at 1 mg/kg per hour)
titrated to a serum sodium of 150 to 155 mmol/L. Side effects of hypertonic
saline include volume overload and pulmonary edema. Hypotension can
occur acutely during bolus dosing of 23.4% saline. In patients with elevated
ICP refractory to the above management strategies, short-term hyperventilation (to PaCO2 25-30 mm Hg), induced hypothermia, or pentobarbital coma may be options. The valsalva maneuver during the second stage
of labor can signicantly increase ICP. Therefore, only a passive second
stage of delivery is recommended when potential elevation in ICP can be
life threatening.
8.4. Prevention
For secondary ischemic stroke prevention, aspirin is considered safe
in pregnancy, whereas there are limited data on other antiplatelet
agents such as clopidogrel or the combination of aspirin and extended
release dipyridamole. For those with ICH or SAH, BP control and
smoking cessation are essential for preventing recurrence. Patients with
a history of aneurysmal SAH and concomitant unruptured aneurysms
should undergo obliterative repair of any additional aneurysms.
8.5. Prognosis
Mortality rates after peripartum stroke range from 4.1% to 14.7%
[54]. The risk of recurrent ischemic stroke is low (1% at 1 year and 2%
at 5 years) [75].
9. Postpartum angiopathy
9.1. Epidemiology
Postpartum angiopathy occurs within the spectrum of reversible
cerebral vasoconstriction syndromes (RCVS), which includes migrainous
1077
vasospasm, Call-Fleming syndrome, and drug-induced cerebral vasoconstriction (typically from cocaine, selective serotonin reuptake inhibitors,
triptans, and amphetamines). It typically presents with thunderclap
headache, confusion, and/or focal neurologic decits. There may be
pathophysiologic similarities between eclampsia, PRES and RCVS, and
often, these entities occur together. Postpartum angiopathy should be
distinguished from primary cerebral angiitis, which is marked by insidious
onset of headache and encephalopathy and primarily affects men [76].
Postpartum angiopathy, when severe, can lead to strokes.
9.2. Diagnosis
Computed tomography, MR, or catheter angiography reveals segmental
narrowing of intracranial arteries that is reversible within days to months on
follow-up imaging. Magnetic resonance imaging may reveal evidence of
infarction. An evaluation for other causes of vasculopathy or vasculitis is
reasonable in these patients. Typical laboratory studies for secondary causes
of vasculopathy in the serum and cerebrospinal uid (CSF) might include
anti-nuclear antibody, double-stranded DNA, extractable nuclear antigen
antibodies, rheumatoid factor, angiotensin-converting enzyme, hepatitis B
and C, Lyme antibodies, cytoplasmic anti-neutrophil cytoplasmic antibody
and perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), syphilis
antibodies/rapid plasma reagin, paraneoplastic antibody screening, cryoglobulins, hemoglobin electrophoresis (for sickle cell disease), complement,
erythrocyte sedimentation rate, c-reactive protein, CSF herpes simplex virus
polymerase chain reaction (PCR), CSF varicella-zoster PCR, CSF cytomegalovirus PCR, CSF arbovirus PCR/antibodies, CSF culture, and CSF cytology.
9.3. Treatment
Although data are limited, oral calcium channel blockers, such as
verapamil (90 mg three times a day), have been used to ameliorate
symptoms of headache and vessel spasm. Although there is no established
denitive treatment, short-term corticosteroids, IV magnesium, intraarterial
calcium channel blockers, and balloon angioplasty have been used in cases
of severe or refractory vasoconstriction [77]. Induced hypertension (with
norepinephrine or phenylephrine) has been used in some instances to
improve cerebral perfusion. Because postpartum angiopathy is considered
part of the spectrum of RCVS, it may also resolve spontaneously [76].
9.4. Prognosis
Although early progressive deterioration has been documented in
some cases, the overall prognosis in small case series is good. Fifty percent
of patients make a complete recovery, whereas 22% in one series had a
fulminant, progressive, and fatal course [77]. The risk of recurrence in
future pregnancies appears to be small [78].
10. Cerebral venous thrombosis
10.1. Epidemiology
Pregnancy induces a hypercoagulable state. Coagulation factors
gradually and signicantly increase during pregnancy. At term,
brinogen reaches 200% and factor VII reaches 1000% of prepregnancy
levels [79]. In addition, there is increased activated protein
C resistance in the second and third trimesters, increased factors II,
VIII, X, XII, and von Willebrand factor and decreased protein S activity.
Elevated levels of estrogen, particularly during the second and third
trimester, stimulate the production of these clotting factors in the
liver. This alone explains only a fraction of CVTs during pregnancy,
which occurs in 11.6 per 100 000 deliveries, accounting for 2%
of pregnancy-related strokes [54,67]. Preexisting thrombophilia,
previous personal history of rst-degree relative with thrombus,
cesarean delivery, hypertension, and infection act as additive risk
factors for CVT in pregnancy [80]. Cerebral venous thrombosis (CVT)
1078
most commonly occurs in the transverse sinus and usually in the third
trimester or immediate postpartum period. Cerebral venous thrombosis may present with headache, vomiting, confusion, blurred vision
(evidence of elevated intracranial pressure), seizure and/or focal
neurologic decits. Complications of CVT include seizures, elevated
intracranial pressure, venous ischemic infarcts, and ICH.
10.2. Diagnosis
The diagnosis of CVT may be made by CT or MR venography or
catheter angiography. To limit radiation exposure, MR venography
is preferred. Magnetic resonance imaging or CT may demonstrate ICH
or venous ischemic infarction. A hypercoagulability evaluation is
advised and typically includes factor V Leiden, prothrombin gene
mutation (G20210A), antithrombin III level, protein C and S activity
and level, and antiphospholipid antibodies (lupus anticoagulant and
anticardiolipin antibodies). Protein C and S and antithrombin III
tested should be deferred for 2 to 4 weeks after completion of
anticoagulation therapy because results are unreliable in the context
of warfarin use [13].
10.3. Treatment
Management of CVT includes treatment of seizures and strokes
related to CVT. The 2014 American Heart Association guidelines
recommend full anticoagulation using full-dose low molecular weight
heparin throughout pregnancy and low molecular weight heparin or a
vitamin K antagonist for a duration of 6 months to a target INR of 2.0
to 3.0 [13,81]. Treatment should continue for at least 6 weeks
postpartum. The presence of ICH is not a contraindication to
anticoagulation in the context of CVT. Women with recurrent CVT,
venous thromboembolism after CVT, or CVT associated with severe
thrombophilia should be considered for indenite anticoagulation
with a goal INR of 2.0 to 3.0 [13]. Unfractionated heparin may be
considered before delivery (particularly if cesarean section is
planned) and can be started at 36-week gestation because it has a
shorter half-life and can be easily monitored. Anticoagulation can be
resumed 6 hours after vaginal delivery and 12 hours after a cesarean
delivery [48].
10.4. Prognosis
In a large series of patients with CVT, in-hospital mortality rate was
4.3%, and the primary cause of death was herniation related to mass
effect from hemorrhage. Twenty-three percent of patients deteriorated after admission [82]. At 16 months, nearly 80% of patients with
CVT have minor symptoms or better in one series [83]. Pregnancy,
puerperum, oral contraceptive, and hormonal replacementrelated
CVT portend a better prognosis than other etiologies [84].
10.5. Prevention
In women with a history of CVT, it is reasonable to prophylax with
low molecular weight heparin during future pregnancies through the
postpartum period [13].
11. Amniotic uid embolism
11.1. Epidemiology
Amniotic uid embolism is rare and occurs in 1 to 12 per 100 000
deliveries but has a high rate of mortality for both the mother and
fetus. Amniotic uid embolism occurs when amniotic uid enters the
maternal circulation after uterine trauma or by iatrogenic or
idiopathic disruption of the endocervical veins or disruption at the
site of placental insertion. Amniotic uid embolism may be, in part, an
immune-mediated response to fetal antigens entering the maternal

circulation via the amniotic uid. Amniotic uid embolism causes a
systemic inammatory reaction leading to pulmonary vasoconstriction, hypoxia, noncardiogenic pulmonary edema, cardiogenic shock,
respiratory failure, DIC, coma and/or seizures (in 10%-20% of cases)
[85]. The AFE course is biphasic with an initial increase in pulmonary
hypertension leading to right then subsequently left ventricular
failure [86]. Paradoxic amniotic uid embolic can cause ischemic
stroke. In addition, prolonged hypoxia or hypotension can lead to
hypoxic ischemic encephalopathy and watershed ischemic strokes.
Clinical symptoms, most commonly catastrophic cardiorespiratory
collapse, typically occur during labor and delivery or in the immediate
postpartum period. Risk factors include maternal age less than 20 or
more than 35 years, forceps-assisted or vacuum-assisted delivery,
cesarean delivery, placenta previa, placental abruption, grand multiparity, cervical lacerations, eclampsia, and fetal distress.
11.2. Diagnosis
Blood samples from the distal port of a pulmonary artery catheter
can show evidence of fetal debris by staining. This is not specic,
however, as such debris can be seen after uncomplicated delivery.
There is emerging evidence that the use of monoclonal antibody to
TKH-2 may be a sensitive test, but this is not universally used, and the
diagnosis of AFE remains a clinical diagnosis [86].
11.3. Treatment
Treatment of AFE is primarily supportive. Fluid resuscitation and
pressor support may be required in the presence of shock. Nitric oxide
or epoprostenol can be considered for treatment of pulmonary
hypertension. In cases of refractory hypoxemia, extracorporeal
membrane oxygenation may be used. Cryoprecipitate may assist in
the removal of amniotic uid debris from the blood [86]. Early
delivery is recommended to improve neonatal outcomes.
11.4. Prognosis
Mortality rates due to AFE are 20% [87]. Indeed, AFE causes 10% of
all maternal deaths in developed nations and is the second most
common cause of death after thrombosis [88]. Among survivors of
AFE, 85% have neurologic injury related to hypoxic ischemic insult,
and neonatal mortality rates range from 20% to 60% [85].
12. Choriocarcinoma
12.1. Epidemiology
Gestational trophoblastic disease refers to a spectrum of conditions after aberrant fertilization, including hydatiform mole, placental
site trophoblastic tumors, epithelioid trophoblastic tumors, and
choriocarcinoma. Choriocarcinoma is a malignant neoplasm that
arises from placental trophoblastic tissue, typically after a molar
pregnancy (1 per 30 mol/L pregnancies and 1 per 50 000 full-term
pregnancies) [89]. Choriocarcinoma causes widespread disease with
metastatic involvement of the lung in 80% of patients and of the brain
in 10% to 25% of patients. By the time metastases reach the brain, most
patients already have metastases to the lung. These metastases are
highly vascular and have a tendency to hemorrhage.
12.2. Diagnosis
Brain MRI reveals evidence of metastases, which are typically
gadolinium enhancing and may have evidence of hemorrhage.
Excessively elevated serum human choriogonadotrophic hormone
levels can give a clue to the diagnoses. Cerebrospinal uid human

chorionic gonadotropin can also be elevated, but the sensitivity of this
test is unclear. Chest imaging is indicated, because the lungs are the
most common site of metastases.
1079
intracranial hemorrhage, TTP-HUS, and sinus thrombosis are managed in a similar fashion to nonpregnant patients, with consideration
being given to minimizing radiation exposure in imaging, tailoring
drug choices to those least teratogenic, and monitoring fetal status
using ultrasound and fetal heart monitoring.
12.3. Treatment
Chemotherapy is the treatment of choice [89]. Options include
monotherapy with methotrexate, dactinomycin, etoposide, or 5uorouracil or multiagent therapy with the combination of etoposide,
methotrexate, and dactinomycin followed by cyclophosphamide
and viscritine.
12.4. Prognosis
Choriocarcinoma is one of the most chemotherapy sensitive and
highly curable tumors, even in the setting of metastases. Patients with
isolated brain metastases have a greater than 50% cure rate, although
the prognosis is poorer if there are concomitant hepatic metastases.
13. Acute fatty liver of pregnancy
13.1. Epidemiology
Acute fatty liver of pregnancy (AFLP) is more common with
multiple gestations and occurs in 5 per 100 000 pregnancies [90].
Acute fatty liver of pregnancy typically occurs during the third
trimester and can present with confusion or encephalopathy
(40%-60%), fever, jaundice (40%-90%), nausea and vomiting, abdominal pain, hypertension (50%), and proteinuria (30%-50%) [34]. Acute
fatty liver of pregnancy can progress to fulminant liver failure
accompanied by hypoglycemia and acute renal failure. The pathogenesis of AFLP may be related to inherited deciencies in
mitochondrial oxidation of long chain fatty acids (long-chain 3hydroxyacyl CoA dehydrogenase deciency).
13.2. Diagnosis
Typical laboratory ndings include elevated transaminases, bilirubin, hypoglycemia, DIC, thrombocytopenia, and impaired renal
function [34]. Liver biopsy reveals microvesicular fatty inltration of
hepatocytes (oil red O stains).
13.3. Treatment
The primary treatment is emergent delivery after maternal
stabilization. Coagulopathy reversal may be required in the context
of active bleeding or before delivery. Liver enzymes and markers of
coagulopathy typically normalize shortly after delivery.
13.4. Prognosis
Maternal mortality rates range from 2% to 12% [90,91]. Most
patients recover without sequelae, and few require transplant with
early diagnosis and delivery. Acute fatty liver of pregnancy can recur
in future pregnancies, even if long-chain 3-hydroxyacyl CoA dehydrogenase deciency mutation is not detected.
14. Conclusions
Neurologic complications of pregnancy can be life threatening if
not recognized and managed promptly. Many of these conditions can
be cured by delivery of the fetus including preeclampsia/eclampsia,
AFLP, and HELLP syndrome. The rst 6 weeks of the postpartum
period is a high-risk time for ischemic and hemorrhagic stroke and
CVT. Most neurologic complications, including seizures, stroke,
References
[1] Selo-Ojeme D, Omosaiye M, Battacharjee P, Kadir R. Risk factors for obstetric
admissions to the intensive care unit in a tertiary hospital: a case-control study.
Arch Gynecol Obstet 2005;272(3):20710. http://dx.doi.org/10.1007/s00404004-0695-x [published Online First: Epub Date].
[2] Pollock W, Rose L, Dennis C-L. Pregnant and postpartum admissions to the intensive
care unit: a systematic review. Intensive Care Med 2010;36(9):146574. http://dx.
doi.org/10.1007/s00134-010-1951-0 [published Online First: Epub Date].
[3] Helms AK, Kittner SJ. Pregnancy and stroke. CNS Spectrum 2005;10(7):5807.
[4] Izci B, Vennelle M, Liston WA, Dundas KC, Calder AA, Douglas NJ. Sleepdisordered breathing and upper airway size in pregnancy and post-partum. Eur
Respir J 2006;27(2):3217. http://dx.doi.org/10.1183/09031936.06.00148204
[published Online First: Epub Date].
[5] Pilkington S, Carli F, Dakin MJ, Romney M, De Witt KA, Dore CJ, et al. Increase in
Mallampati score during pregnancy. Br J Anaesth 1995;74(6):63842.
[6] Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized
controlled trials of ephedrine versus phenylephrine for the management of
hypotension during spinal anesthesia for cesarean delivery. Anesth Analg
2002;94(4):9206 [table of contents].
[7] Practice ACoO. ACOG Committee Opinion. Number 299, September 2004
(replaces No. 158, September 1995). Guidelines for diagnostic imaging during
pregnancy. Obstet Gynecol 2004;104(3):64751.
[8] ACOG Committee Opinion. Number 299, September 2004 (replaces No. 158,
September 1995). Guidelines for diagnostic imaging during pregnancy. Obstet
Gynecol 2004;104(3):64751.
[9] Kochi MH, Kaloudis EV, Ahmed W, Moore WH. Effect of in utero exposure of
iodinated intravenous contrast on neonatal thyroid function. J Comput Assist
Tomogr 2012;36(2):1659. http://dx.doi.org/10.1097/RCT.0b013e31824cc048
[10] Mehta PS, Mehta SJ, Vorherr H. Congenital iodide goiter and hypothyroidism: a
review. Obstet Gynecol Surv 1983;38(5):23747.
[11] Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in the rates of
preeclampsia, eclampsia, and gestational hypertension, United States, 19872004. Am J Hypertens 2008;21(5):5216. http://dx.doi.org/10.1038/ajh.2008.20
[12] Maynard SE, Karumanchi SA. Angiogenic factors and preeclampsia. Semin Nephrol
2011;31(1):3346. http://dx.doi.org/10.1016/j.semnephrol.2010.10.004 [published
Online First: Epub Date].
[13] Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, et al.
Guidelines for the prevention of stroke in women: a statement for Healthcare
Professionals From the American Heart Association/American Stroke Association.
Stroke 2014. http://dx.doi.org/10.1161/01.str.0000442009.06663.48 [published
[14] Schroeder BM. ACOG practice bulletin on diagnosing and managing preeclampsia
and eclampsia. American College of Obstetricians and Gynecologists. Am Fam
Physician 2002;66(2):3301.
[15] Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F, Marcoux S, et al. Prevention
of preeclampsia and intrauterine growth restriction with aspirin started in early
pregnancy: a meta-analysis. Obstet Gynecol 2010;116(2 Pt. 1):40214. http://dx.
doi.org/10.1097/AOG.0b013e3181e9322a [published Online First: Epub Date].
[16] Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of
cardiovascular disease and cancer in later life: systematic review and metaanalysis. BMJ 2007;335(7627):974. http://dx.doi.org/10.1136/
bmj.39335.385301.BE [published Online First: Epub Date].
[17] McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular
sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses.
Am Heart J 2008;156(5):91830. http://dx.doi.org/10.1016/j.ahj.2008.06.042
[18] Brown MC, Best KE, Pearce MS, Waugh J, Robson SC, Bell R. Cardiovascular
disease risk in women with pre-eclampsia: systematic review and meta-analysis.
Eur J Epidemiol 2013;28(1):119. http://dx.doi.org/10.1007/s10654-013-97626 [published Online First: Epub Date].
[19] Berks D, Hoedjes M, Raat H, Duvekot JJ, Steegers EA, Habbema JD. Risk of
cardiovascular disease after pre-eclampsia and the effect of lifestyle interventions: a
literature-based study. BJOG 2013;120(8):92431. http://dx.doi.org/10.1111/
1471-0528.12191 [published Online First: Epub Date].
[20] Oehm E, Hetzel A, Els T, Berlis A, Keck C, Will HG, et al. Cerebral hemodynamics
and autoregulation in reversible posterior leukoencephalopathy syndrome
caused by pre-/eclampsia. Cerebrovasc Dis 2006;22(2-3):2048. http://dx.doi.
org/10.1159/000093810 [published Online First: Epub Date].
[21] Beausang-Linder M, Bill A. Cerebral circulation in acute arterial hypertensionprotective
effects of sympathetic nervous activity. Acta Physiol Scand 1981;111(2):1939. http://dx.
doi.org/10.1111/j.1748-1716.1981.tb06724.x [published Online First: Epub Date].
[22] Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior
leukoencephalopathy syndrome. N Engl J Med 1996;334(8):494500. http://dx.doi.
org/10.1056/NEJM199602223340803 [published Online First: Epub Date].
1080
[23] Schaefer PW, Buonanno FS, Gonzalez RG, Schwamm LH. Diffusion-weighted
imaging discriminates between cytotoxic and vasogenic edema in a patient with
eclampsia. Stroke 1997;28(5):10825.
[24] Easterling TR, Brateng D, Schmucker B, Brown Z, Millard SP. Prevention of
preeclampsia: a randomized trial of atenolol in hyperdynamic patients before
onset of hypertension. Obstet Gynecol 1999;93(5 Pt. 1):72533.
[25] Magee LA, Duley L. Oral beta-blockers for mild to moderate hypertension during
pregnancy. Cochrane Database Syst Rev 2003(3):CD002863. http://dx.doi.org/
10.1002/14651858.CD002863 [published Online First: Epub Date].
[26] Emergent therapy for acute-onset, severe hypertension with preeclampsia or
eclampsia. Obstet Gynecol 2011;118(6):14658.
[27] Which anticonvulsant for women with eclampsia? Evidence from the Collaborative
Eclampsia Trial. Lancet 1995;345(8963):145563.
[28] Sibai BM, Caritis SN, Thom E, Klebanoff M, McNellis D, Rocco L, et al. Prevention of
preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The
National Institute of Child Health and Human Development Network of MaternalFetal Medicine Units. N Engl J Med 1993;329(17):12138. http://dx.doi.org/
10.1056/NEJM199310213291701 [published Online First: Epub Date].
[29] Caritis S, Sibai B, Hauth J, Lindheimer MD, Klebanoff M, Thom E, et al. Low-dose
aspirin to prevent preeclampsia in women at high risk. National Institute of Child
Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl
J Med 1998;338(11):7015. http://dx.doi.org/10.1056/NEJM199803123381101
[30] Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing
pre-eclampsia and its complications. Cochrane Database Syst Rev 2007(2):
CD004659. http://dx.doi.org/10.1002/14651858.CD004659.pub2 [published
[31] Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO.
Recommendations for prophylaxis of pregnancy-related venous thromboembolism
in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines: a
rebuttal. J Thromb Haemost 2013. http://dx.doi.org/10.1111/jth.12347 [published
[32] Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L. Calcium supplementation during
pregnancy for preventing hypertensive disorders and related problems.
Cochrane Database Syst Rev 2010(8):CD001059. http://dx.doi.org/10.1002/
14651858.CD001059.pub3 [published Online First: Epub Date].
[33] Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol
2009;33(3):1307. http://dx.doi.org/10.1053/j.semperi.2009.02.010 [published
[34] Sibai BM. Imitators of severe pre-eclampsia. Semin Perinatol 2009;33(3):196205.
http://dx.doi.org/10.1053/j.semperi.2009.02.004 [published Online First: Epub
Date].
[35] Fonseca JE, Mendez F, Catano C, Arias F. Dexamethasone treatment does not
improve the outcome of women with HELLP syndrome: a double-blind, placebocontrolled, randomized clinical trial. Am J Obstet Gynecol 2005;193(5):15918.
http://dx.doi.org/10.1016/j.ajog.2005.07.037 [published Online First: Epub Date].
[36] Warren JE, Simonsen SE, Branch DW, Porter TF, Silver RM. Thromboprophylaxis and
pregnancy outcomes in asymptomatic women with inherited thrombophilias. Am J
Obstet Gynecol 2009;200(3):281.e15. http://dx.doi.org/10.1016/j.ajog.2008.10.021
[37] Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal
morbidity and mortality in 442 pregnancies with hemolysis, elevated liver
enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol 1993;169
(4):10006.
[38] Dashe JS, Ramin SM, Cunningham FG. The long-term consequences of thrombotic
microangiopathy (thrombotic thrombocytopenic purpura and hemolytic uremic
syndrome) in pregnancy. Obstet Gynecol 1998;91(5 Pt. 1):6628.
[39] Ezra Y, Rose M, Eldor A. Therapy and prevention of thrombotic thrombocytopenic purpura during pregnancy: a clinical study of 16 pregnancies. Am J
Hematol 1996;51(1):16. http://dx.doi.org/10.1002/(SICI)1096-8652(199601)
51:1b1::AID-AJH1N3.0.CO;2-2 [published Online First: Epub Date].
[40] George JN. The association of pregnancy with thrombotic thrombocytopenic
purpura-hemolytic uremic syndrome. Curr Opin Hematol 2003;10(5):33944.
[41] Swisher KK, Terrell DR, Vesely SK, Kremer Hovinga JA, Lammle B, George JN.
Clinical outcomes after platelet transfusions in patients with thrombotic
thrombocytopenic purpura. Transfusion 2009;49(5):87387. http://dx.doi.org/
10.1111/j.1537-2995.2008.02082.x [published Online First: Epub Date].
[42] Nguyen L, Terrell DR, Duvall D, Vesely SK, George JN. Complications of plasma
exchange in patients treated for thrombotic thrombocytopenic purpura. IV. An
additional study of 43 consecutive patients, 2005 to 2008. Transfusion 2009;49
(2):3924. http://dx.doi.org/10.1111/j.1537-2995.2008.02030.x [published Online
First: Epub Date].
[43] May Jr HV, Harbert Jr GM, Thornton Jr WN. Thrombotic thrombocytopenic
purpura associated with pregnancy. Am J Obstet Gynecol 1976;126(4):4528.
[44] Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, et al.
Comparison of plasma exchange with plasma infusion in the treatment of
thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl
J Med 1991;325(6):3937. http://dx.doi.org/10.1056/NEJM199108083250604
[45] Michael M, Elliott EJ, Ridley GF, Hodson EM, Craig JC. Interventions for
haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura.
Cochrane Database Syst Rev 2009(1):CD003595. http://dx.doi.org/10.1002/
14651858.CD003595.pub2 [published Online First: Epub Date].
[46] Noe KH, Pack AM. Women issues and epilepsy. Continuum 2010;16(3):15978.
[47] APPENDIX C: AAN summary of evidence-based guidelines for clinicians: management issues for women with epilepsy-teratogenesis and perinatal outcomes.
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
[57]
[58]
[59]
[60]
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68]
[69]
Continuum (Minneap Minn) 2010;16(3):2602. http://dx.doi.org/10.1212/01.

CON.0000368247.02976.ad [Epilepsy, published Online First: Epub Date].
Sheth SS, Sheth KN. Treatment of neurocritical care emergencies in pregnancy.
Curr Treat Options Neurol 2012. http://dx.doi.org/10.1007/s11940-011-0161-6
Mawhinney E, Craig J, Morrow J, Russell A, Smithson WH, Parsons L, et al.
Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and
pregnancy registers. Neurology 2013;80(4):4005. http://dx.doi.org/10.1212/
WNL.0b013e31827f0874 [published Online First: Epub Date].
Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. Guidelines
for the evaluation and management of status epilepticus. Neurocrit Care 2012;17
(1):323. http://dx.doi.org/10.1007/s12028-012-9695-z [published Online First:
Epub Date].
Kuhnz W, Koch S, Helge H, Nau H. Primidone and phenobarbital during lactation
period in epileptic women: total and free drug serum levels in the nursed infants
and their effects on neonatal behavior. Dev Pharmacol Ther 1988;11(3):14754.
Meador KJ, Pennell PB, Harden CL, Gordon JC, Tomson T, Kaplan PW, et al.
Pregnancy registries in epilepsy a consensus statement on health outcomes.
Neurology 2008;71(14):110917.
Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, et al. Practice
parameter update: management issues for women with epilepsyfocus on
pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and
breastfeeding report of the Quality Standards Subcommittee and Therapeutics
and Technology Assessment Subcommittee of the American Academy of
Neurology and American Epilepsy Society; 2009 1429.
James AH, Bushnell CD, Jamison MG, Myers ER. Incidence and risk factors for stroke in
pregnancy and the puerperium. Obstet Gynecol 2005;106(3):50916. http://dx.doi.
org/10.1097/01.AOG.0000172428.78411.b0 [published Online First: Epub Date].
Lidegaard O, Lokkegaard E, Jensen A, Skovlund CW, Keiding N. Thrombotic stroke and
myocardial infarction with hormonal contraception. N Engl J Med 2012;366
(24):225766. http://dx.doi.org/10.1056/NEJMoa1111840 [published Online First:
Epub Date].
Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MS. Risk of a
thrombotic event after the 6-week postpartum period. N Engl J Med 2014;370
(14):130715. http://dx.doi.org/10.1056/NEJMoa1311485 [published Online
First: Epub Date].
Tiel Groenestege AT, Rinkel GJ, van der Bom JG, Algra A, Klijn CJ. The risk of
aneurysmal subarachnoid hemorrhage during pregnancy, delivery, and the
puerperium in the Utrecht population: case-crossover study and standardized
incidence ratio estimation. Stroke 2009;40(4):114851. http://dx.doi.org/
10.1161/strokeaha.108.539700 [published Online First: Epub Date].
Marshman LA, Aspoas AR, Rai MS, Chawda SJ. The implications of ISAT and ISUIA
for the management of cerebral aneurysms during pregnancy. Neurosurg Rev
2007;30(3):17780. http://dx.doi.org/10.1007/s10143-007-0074-8 [discussion
80, published Online First: Epub Date].
Horton JC, Chambers WA, Lyons SL, Adams RD, Kjellberg RN. Pregnancy and the
risk of hemorrhage from cerebral arteriovenous malformations. Neurosurgery
1990;27(6):86771 [discussion 712].
Bateman BT, Schumacher HC, Bushnell CD, Pile-Spellman J, Simpson LL, Sacco RL,
et al. Intracerebral hemorrhage in pregnancy: frequency, risk factors, and
outcome. Neurology 2006;67(3):4249. http://dx.doi.org/10.1212/01.
wnl.0000228277.84760.a2 [published Online First: Epub Date].
Scott CA, Bewley S, Rudd A, Spark P, Kurinczuk JJ, Brocklehurst P, et al. Incidence, risk
factors, management, and outcomes of stroke in pregnancy. Obstet Gynecol
2012;120(2 Pt. 1):31824. http://dx.doi.org/10.1097/AOG.0b013e31825f287c
Tang CH, Wu CS, Lee TH, Hung ST, Yang CY, Lee CH, et al. Preeclampsia-eclampsia and
the risk of stroke among peripartum in Taiwan. Stroke 2009;40(4):11628. http://dx.
doi.org/10.1161/STROKEAHA.108.540880 [published Online First: Epub Date].
Jauch EC, Saver JL, Adams Jr HP, Bruno A, Connors JJ, Demaerschalk BM, et al.
Guidelines for the early management of patients with acute ischemic stroke: a
guideline for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke 2013;44(3):870947. http://dx.doi.org/
10.1161/STR.0b013e318284056a [published Online First: Epub Date].
Wiese KM, Talkad A, Mathews M, Wang D. Intravenous recombinant tissue
plasminogen activator in a pregnant woman with cardioembolic stroke. Stroke
2006;37(8):21689. http://dx.doi.org/10.1161/01.STR.0000230286.95513.c2
Leonhardt G, Gaul C, Nietsch HH, Buerke M, Schleussner E. Thrombolytic therapy
in pregnancy. J Thromb Thrombolysis 2006;21(3):2716. http://dx.doi.org/
10.1007/s11239-006-5709-z [published Online First: Epub Date].
Chase C, Sullivan C. Neurocritical illness during pregnancy and puerperium. In:
Bhardwaj A, Mirski MA, editors. Handbook of Neurocritical Care. Springer New
York; 2010. p. 52331.
Tettenborn B. Stroke and pregnancy. Neurol Clin 2012;30(3):91324. http://dx.
doi.org/10.1016/j.ncl.2012.06.002 [published Online First: Epub Date].
Molyneux A, Kerr R, Stratton I, Sandercock P, Clarke M, Shrimpton J, et al.
International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping
versus endovascular coiling in 2143 patients with ruptured intracranial
aneurysms: a randomised trial. Lancet 2002;360(9342):126774.
Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, et al. International
subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a
randomised comparison of effects on survival, dependency, seizures, rebleeding,
subgroups, and aneurysm occlusion. Lancet 2005;366(9488):80917. http://dx.
doi.org/10.1016/s0140-6736(05)67214-5 [published Online First: Epub Date].

[70] McDougall CG, Spetzler RF, Zabramski JM, Partovi S, Hills NK, Nakaji P, et al. The
Barrow Ruptured Aneurysm Trial. J Neurosurg 2012;116(1):13544. http://dx.
doi.org/10.3171/2011.8.jns101767 [published Online First: Epub Date].
[71] Stoodley MA, Macdonald RL, Weir BK. Pregnancy and intracranial aneurysms.
Neurosurg Clin N Am 1998;9(3):54956.
[72] Slichter SJ, Kaufman RM, Assmann SF, McCullough J, Triulzi DJ, Strauss RG, et al.
Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl
J Med 2010;362(7):60013. http://dx.doi.org/10.1056/NEJMoa0904084 [published Online First: Epub Date].
[73] Rebulla P, Finazzi G, Marangoni F, Avvisati G, Gugliotta L, Tognoni G, et al. The
threshold for prophylactic platelet transfusions in adults with acute myeloid
leukemia. Gruppo Italiano Malattie Ematologiche Maligne dellAdulto. N Engl J
Med 1997;337(26):18705. http://dx.doi.org/10.1056/NEJM199712253372602
[74] Wandt H, Schaefer-Eckart K, Wendelin K, Pilz B, Wilhelm M, Thalheimer M, et al.
Therapeutic platelet transfusion versus routine prophylactic transfusion in
patients with haematological malignancies: an open-label, multicentre, randomised study. Lancet 2012;380(9850):130916. http://dx.doi.org/10.1016/
S0140-6736(12)60689-8 [published Online First: Epub Date].
[75] Lamy C, Hamon JB, Coste J, Mas JL. Ischemic stroke in young women: risk of
recurrence during subsequent pregnancies. French Study Group on Stroke in
Pregnancy. Neurology 2000;55(2):26974.
[76] Singhal AB, Bernstein RA. Postpartum angiopathy and other cerebral vasoconstriction syndromes. Neurocrit Care 2005;3(1):917. http://dx.doi.org/10.1385/
NCC:3:1:091 [published Online First: Epub Date].
[77] Fugate JE, Ameriso SF, Ortiz G, Schottlaender LV, Wijdicks EF, Flemming KD, et al.
Variable presentations of postpartum angiopathy. Stroke 2012;43(3):6706. http://dx.
doi.org/10.1161/STROKEAHA.111.639575 [published Online First: Epub Date].
[78] Remi J, Pfefferkorn T, Fesl G, Rogenhofer N, Straube A, Klein M. Uncomplicated
pregnancy and delivery after previous severe postpartum cerebral angiopathy.
Case reports in neurology, 3(3); 2011. p. 2527. http://dx.doi.org/10.1159/
000333782 [published Online First: Epub Date].
[79] Maybury H, Squire P, Pierik F, Pavord S, Taylor DJ. The hypercoagulable state of
pregnancy: reference range of thromboelastographic parameters in normal
pregnancy. BJOG 2006;113(7):8567.
[80] Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. N Engl J Med
2008;359(19):202533. http://dx.doi.org/10.1056/NEJMra0707993 [published
[81] Furie KL. Introduction for advances in stroke 2011. Stroke 2012;43(2):297.
http://dx.doi.org/10.1161/strokeaha.111.647735 [published Online First:
Epub Date].
[82] Canhao P, Ferro JM, Lindgren AG, Bousser MG, Stam J, Barinagarrementeria F,
et al. Causes and predictors of death in cerebral venous thrombosis. Stroke
2005;36(8):17205. http://dx.doi.org/10.1161/01.STR.0000173152.84438.1c
[83] Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F, Investigators I.
Prognosis of cerebral vein and dural sinus thrombosis: results of the International
Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35
(3):66470. http://dx.doi.org/10.1161/01.STR.0000117571.76197.26 [published
[84] Coutinho JM, Ferro JM, Canhao P, Barinagarrementeria F, Cantu C, Bousser MG,
et al. Cerebral venous and sinus thrombosis in women. Stroke 2009;40
(7):235661. http://dx.doi.org/10.1161/STROKEAHA.108.543884 [published
[85] Clark SL, Hankins GD, Dudley DA, Dildy GA, Porter TF. Amniotic uid embolism:
analysis of the national registry. Am J Obstet Gynecol 1995;172(4 Pt. 1):115867
[discussion 679].
[86] Conde-Agudelo A, Romero R. Amniotic uid embolism: an evidence-based
review. Am J Obstet Gynecol 2009;201(5):445.e1445.e13. http://dx.doi.org/
10.1016/j.ajog.2009.04.052 [published Online First: Epub Date].
1081
[87] Kramer MS, Rouleau J, Baskett TF, Joseph KS. Amniotic-uid embolism and
medical induction of labour: a retrospective, population-based cohort study.
Lancet 2006;368(9545):14448. http://dx.doi.org/10.1016/s0140-6736(06)
69607-4 [published Online First: Epub Date].
[88] Berg CJ, Callaghan WM, Syverson C, Henderson Z. Pregnancy-related mortality in
the United States, 1998 to 2005. Obstet Gynecol 2010;116(6):13029. http://dx.
doi.org/10.1097/AOG.0b013e3181fdfb11 [published Online First: Epub Date].
[89] Berkowitz RS, Goldstein DP. Chorionic tumors. N Engl J Med 1996;335(23):17408.
http://dx.doi.org/10.1056/NEJM199612053352306 [published Online First: Epub
Date].
[90] Knight M, Nelson-Piercy C, Kurinczuk JJ, et al, System UKOS. A prospective
national study of acute fatty liver of pregnancy in the UK. Gut 2008;57(7):9516.
http://dx.doi.org/10.1136/gut.2008.148676 [published Online First: Epub Date].
[91] Pereira SP, ODonohue J, Wendon J, Williams R. Maternal and perinatal outcome
in severe pregnancy-related liver disease. Hepatology 1997;26(5):125862.
http://dx.doi.org/10.1002/hep.510260525 [published Online First: Epub Date].
[92] Jun Zhang SM, Trumble Ann. Severe Maternal Morbidity Associated with
Hypertensive Disorders in Pregnancy in the United States, 22(2); 2003.
[93] Weinreb HJ. Demyelinating and neoplastic diseases in pregnancy. Neurol Clin
1994;12(3):50926.
[94] Klein A. Peripheral nerve disease in pregnancy. Clin Obstet Gynecol 2013;56(2):3828.
http://dx.doi.org/10.1097/GRF.0b013e31828f260e [published Online First: Epub Date].
[95] Varner M. Myasthenia gravis and pregnancy. Clin Obstet Gynecol 2013;56
(2):37281. http://dx.doi.org/10.1097/GRF.0b013e31828e92c0 [published
[96] Kittner SJ, Stern BJ, Feeser BR, Hebel R, Nagey DA, Buchholz DW, et al. Pregnancy
and the risk of stroke. N Engl J Med 1996;335(11):76874. http://dx.doi.org/
10.1056/nejm199609123351102 [published Online First: Epub Date].
[97] Finkelsztejn A, Brooks JB, Paschoal Jr FM, Fragoso YD. What can we really tell
women with multiple sclerosis regarding pregnancy? A systematic review and
meta-analysis of the literature. BJOG 2011;118(7):7907. http://dx.doi.org/
10.1111/j.1471-0528.2011.02931.x [published Online First: Epub Date].
[98] Kranick SM, Mowry EM, Colcher A, Horn S, Golbe LI. Movement disorders and
pregnancy: a review of the literature. Mov Disord 2010;25(6):66571. http://dx.
doi.org/10.1002/mds.23071 [published Online First: Epub Date].
[99] Roelvink NC, Kamphorst W, van Alphen HA, Rao BR. Pregnancy-related primary
brain and spinal tumors. Arch Neurol 1987;44(2):20915.
[100] Cusimano MD, Meffe FM, Gentili F, Sermer M. Ventriculoperitoneal shunt
malfunction during pregnancy. Neurosurgery 1990;27(6):96971.
[101] Liu S, Joseph KS, Liston RM, Bartholomew S, Walker M, Leon JA, et al. Incidence, risk
factors, and associated complications of eclampsia. Obstet Gynecol 2011;118
(5):98794. http://dx.doi.org/10.1097/AOG.0b013e31823311c1 [published Online
First: Epub Date].
[102] Martin Jr JN, Bailey AP, Rehberg JF, Owens MT, Keiser SD, May WL. Thrombotic
thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol
2008;199(2):98104. http://dx.doi.org/10.1016/j.ajog.2008.03.011 [published Online
First: Epub Date].
[103] Hart LA, Sibai BM. Seizures in pregnancy: epilepsy, eclampsia, and stroke. Semin
Perinatol 2013;37(4):20724. http://dx.doi.org/10.1053/j.semperi.2013.04.001
[104] Feske SK. Stroke in pregnancy. Semin Neurol 2007;27(5):44252. http://dx.doi.
org/10.1055/s-2007-991126 [published Online First: Epub Date].
[105] Callaghan WM. Overview of maternal mortality in the United States. Semin
Perinatol 2012;36(1):26. http://dx.doi.org/10.1053/j.semperi.2011.09.002
[106] Saposnik G, Barinagarrementeria F, Brown RD, Bushnell CD, Cucchiara B,
Cushman M, et al. Diagnosis and Management of Cerebral Venous Thrombosis:
A Statement for Healthcare Professionals From the American Heart Association/
American Stroke Association. Stroke 2011;42(4):115892. http://dx.doi.org/
10.1161/STR.0b013e31820a8364 [published Online First: Epub Date].
2014 Elsevier

Neurocritical Care Complications of Pregnancy and Puerperum

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Neurocritical Care Complications of Pregnancy and Puerperum

Uploaded by

Copyright:

Available Formats

Journal of Critical Care 29 (2014) 10691081

Contents lists available at ScienceDirect

Journal of Critical Care

Neurocritical care complications of pregnancy and puerperum

Cerebrovascular Center of the Neurological Institute, Cleveland Clinic, Cleveland, Ohio

2. General critical care considerations

Second, in mechanically ventilated pregnant patients, the target

J.A. Frontera, W. Ahmed / Journal of Critical Care 29 (2014) 10691081

preeclampsia, rst pregnancy, chronic renal disease, inherited

J.A. Frontera, W. Ahmed / Journal of Critical Care 29 (2014) 10691081

receptor blockers, and direct renin inhibitors are contraindicated in

Thrombotic thrombocytopenic purpura and hemolytic uremic

J.A. Frontera, W. Ahmed / Journal of Critical Care 29 (2014) 10691081

Eclampsia occurs in 1/1000 deliveries [92]

Increased lumbar lordosis

Meralgia paresthetica (lateral

Preeclampsia (Bell palsy)

Transplacental passage of IgG

Postpartum exacerbations occur in 30% of

Relative risk 0.7 during pregnancy (not

Assisted reproductive technology

History of frequent MS relapses before

Increased intraabdominal pressure due to

Carpal tunnel occurs in 2%-35% of

Metastases from choriocarcinoma

The following tumors may enlarge

Relative risk 2.5 during pregnancy and

No increased risk of SAH (due to

Occurs during the second-fth month of

J.A. Frontera, W. Ahmed / Journal of Critical Care 29 (2014) 10691081

recommended for early detection. Prophylactic plasma exchange,

(Both of the following met)

(Mild preeclampsia plus one or more of the following)

(All below criteria met)

New onset elevated BP on at least 2 separate

Preeclampsia criteria met

Proteinuria 0.3 g in a 24-h urine specimen

New onset generalized tonic-clonic seizures

Absence of other neurologic conditions that

J.A. Frontera, W. Ahmed / Journal of Critical Care 29 (2014) 10691081

Incidence and mortality

Most common cause

Potential neurologic complications

1.6-10 cases per 10 000 deliveries in

Placental underperfusion and hypoxia

Seizures, ICH, ischemic stroke, PRES,

20th week of gestation up to

Seizure, headaches, encephalopathy, ICH,

Higher risk in localization-related

11.4 per 100 000 deliveries

Rare, although catastrophic and

17% of maternal death [105].

Uterine atony, placental abruption, or

Fetal hypoxia and congenital anomalies

Ischemic or hemorrhagic stroke, seizures,

Typically during delivery or

Abbreviation: US, United States.

bind to protein including phenytoin, valproic acid, carbamezapime,

to seizure suppression or burst suppression) over propofol due to

J.A. Frontera, W. Ahmed / Journal of Critical Care 29 (2014) 10691081

Hypertensive emergencies, preeclampia, eclampsia

Stabilization and delivery of the fetus/placenta in the case of preeclampsia/eclampsia

Steroids do not improve maternal outcome [35,36]

First line: labetalol or hydralazine IV push