CONTENTS

• General
  • Differential diagnosis
  • Initial approach
• Specific information about disease states in pregnancy
  • Acute ischemic stroke
  • Intracranial hemorrhage
  • Seizures
  • Cerebral edema
  • Myasthenia Gravis (MG)
  • Metastatic choriocarcinoma
  • Ventriculoperitoneal shunt malfunction
• Podcast
• Questions & discussion
• Pitfalls

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differential diagnosis

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neurological emergencies encountered in pregnancy

• 💡 Pregnant women presenting with neurologic emergencies can have several simultaneous neuropathologies (especially preeclampsia, PRES, and RCVS).  Thus, detection of one pathology doesn't exclude the possibility of additional simultaneous problems.(27741996)
• (Pre)Eclampsia 📖  & PRES (Posterior Reversible Encephalopathy Syndrome) 📖
  • Preeclampsia is the most common cause of ICU admission in the obstetric population, so this possibility should always be considered.
  • Consider preeclampsia in patients >20 weeks gestation who have Bp >160/110 for 15 minutes, or >140/90 for four hours (diagnostic criteria are shown here: 📖).
  • In the context of pregnancy, PRES is frequently caused by preeclampsia – so these pathologies frequently coexist.
• Reversible Cerebral Vasoconstriction Syndrome (RCVS) 📖
• Cerebral venous thrombosis (CVT) 📖
• Acute ischemic stroke 📖
• Acute hemorrhagic stroke 📖
• Seizure 📖
• Less common conditions:
  • Pituitary apoplexy.
  • Cervical artery dissection.
  • Choriocarcinoma 📖.
  • Amniotic fluid embolism, or air embolism.
  • Thrombotic thrombocytopenic purpura (TTP) 📖
  • Atypical hemolytic uremic syndrome (aHUS) 📖
  • Myasthenia gravis in pregnancy 📖.
  • Wernicke's encephalopathy (may result from hyperemesis gravidarum).📖

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initial approach

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ICU admission laboratory panel for pregnant patient

• (Pregnant patients admitted to ICU often have numerous pathologies – for example preeclampsia, HELLP syndrome, and DIC.  It's easier to be thorough than smart, so starting off with a broad lab panel is advisable.)
• Blood count, electrolytes including Ca/Mg/Phos.
• INR, PTT, fibrinogen, D-dimer, LDH, haptoglobin.
• Liver function tests, ammonia.
• If infection suspected:  appropriate cultures.
• Urinalysis and spot protein/creatinine ratio.
• Useful reference on normal lab values in pregnancy:  Perinatology.com.  

neuroimaging

• CT scan provides very low fetal exposure to radiation and should be performed if indicated (either with or without IV contrast).(33896537; 27741996)
  • Iodinated contrast is considered safe in pregnancy.(33896537, 34177249)
  • ⚠️ Stroke is the cause of one in seven maternal deaths.(27741996)  Imaging should not be delayed in critically ill patients due to concerns regarding radiation exposure.
  • (There has been a shift in practice away from abdominal shielding with more modern CT scanners.(34177249)  Institutional protocols should be utilized, under the supervision of the radiology department.)
• MRI has some advantages over CT, since it provides high-resolution imaging of the brain.(34177249)  However, MRI often cannot be obtained in an emergent fashion.
  • ⚠️ Gadolinium contrast is usually avoided in pregnancy, because the risk to the fetus is unclear.(33896537)  However, gadolinium may be safely utilized while breast feeding.(34177249, 30470268)
  • Noncontrast MR venography (MRV) should be routinely obtained in pregnant patients.(33896537)  This involves MRI sequences which evaluate the venous system without using gadolinium contrast (e.g., using time-of-flight).  Venography is important to evaluate for cerebral venous thrombosis.

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acute ischemic stroke in pregnancy

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Pregnancy increases the risk of acute ischemic stroke roughly ninefold.(33896537)

causes of stroke in pregnancy include: (32487899, 31761061)

• Cardioembolic stroke (including due to peripartum cardiomyopathy).
• Preeclampsia/eclampsia.
• Reversible cerebral vasoconstriction syndrome (RCVS).
• Cerebral venous thrombosis (CVT).
• Cervical arterial dissection.
• Paradoxical embolism, due to venous thromboembolic disease.
• Amniotic fluid emboli.
• Choriocarcinoma with metastases to the brain.
• Antiphospholipid antibody syndrome.

management is similar to that of the non-pregnant patient

• ⚠️ Activate the stroke team.
• Pregnancy is a relative contraindication to thrombolysis, with very scarce data regarding its safety in pregnancy.(33896537)  As always, decisions regarding thrombolysis will be made by the stroke neurology team.
• Endovascular therapy appears to be safe and effective for patients with large vessel occlusion.(33896537)  
• Aspirin is Category B in pregnancy and should be used as it would be in other patients.(34177249)  

investigation of cause

• Given the variety of underlying pathologies which may cause stroke, investigation for an underlying cause should be thorough.  For example:
  • Preeclampsia should always be considered and investigated.
  • Transthoracic echocardiography should be performed to evaluate for underlying peripartum cardiomyopathy.  A bubble study with the echocardiogram may also help evaluate for paradoxical embolization.
  • Additional neuroimaging may be needed to evaluate for cervical artery dissection or cerebral venous thrombosis.

More on acute ischemic stroke here 📖.

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intracranial hemorrhage in pregnancy

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more common causes:

• Eclampsia (e.g., with related PRES or RCVS).
• Cerebral venous thrombosis (CVT).
• Subarachnoid hemorrhage:
  • Basal subarachnoid hemorrhage suggests an aneurysm (which may expand and rupture during pregnancy).  These are most common in the third trimester.(33896537)
  • Convexity subarachnoid hemorrhage may reflect underlying Reversible Cerebral Vasoconstriction Syndrome (RCVS) or Cerebral Venous Thrombosis (CVT).(27741996)  
• Arteriovenous malformations (AVMs).
• Cerebral cavernous malformations (CCMs).

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seizures in pregnancy

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more common causes include:

• Breakthrough seizure in the context of known epilepsy (may result from inadequate medication levels due to increased clearance or distribution).  For example, during pregnancy: (Louis 2021)
  • Lamotrigine levels decrease due to estrogen-induced glucuronidation.
  • Concentrations of levetiracetam, oxcarbazepine, and topiramate decrease.
  • Albumin levels decrease so measurement of free drug levels may be important for highly protein-bound medications (e.g., carbamazepine, phenytoin, valproate).
• Hypoglycemia.
• Eclampsia (including eclampsia-related PRES).
• Cerebral vein thrombosis (CVT).
• Reversible Cerebral Vasoconstriction Syndrome (RCVS).
• Thrombotic Thrombocytopenic Purpura (TTP) or atypical Hemolytic Uremic Syndrome (aHUS).
• Intracranial hemorrhage.
• Intoxication or withdrawal.
• Adverse medication effects.
• Trauma.
• Acute metabolic derangement.
• Intracranial infection.
• Additional causes of seizure: 📖

evaluation

• This is generally similar to the evaluation of seizures in general.📖
• There should be a high index of suspicion for eclampsia in patients between 20 weeks of gestation and 6 weeks postpartum.  More on the diagnostic criteria for eclampsia here.📖

general management

• For ongoing convulsive seizures lasting >5 minutes, the front-line agents remain benzodiazepine (e.g., lorazepam 0.1 mg/kg IV or midazolam 10 mg IM).
• In eclampsia, magnesium is the preferred front-line antiseizure medication (with a bolus and infusion used to prevent seizure recurrence).📖  If it is unclear whether the seizure is due to eclampsia, it may be reasonable to administer both magnesium and a conventional antiseizure medication (e.g., levetiracetam).
• Selection of antiseizure medications is different in the context of pregnancy:
  • Levetiracetam 💉 is generally a front-line choice.(33896537)  
  • Fosphenytoin and especially valproic acid are contraindicated in pregnancy.
  • More on the teratogenicity of antiseizure medications is below.
• Selection of anesthetic infusion for refractory status epilepticus:
  • Propofol is Class B.(33896537)  Propofol is often a preferred agent here in general, so it may be especially preferred in the context of pregnancy.
  • Midazolam is Class C.(33896537)  Midazolam may be utilized in contexts where propofol cannot be given (e.g., refractory shock or severe hypertriglyceridemia).
  • Pentobarbital is Class D, so this should be avoided if possible.
• More on the management of status epilepticus: 📖

antiseizure medication teratogenicity

• Ideally, decisions regarding teratogenicity should be made in conjunction with neurologists and obstetricians.  However, in emergent situations there may not always be enough time to obtain such consultation.(35393968)
• Levetiracetam 💉 is generally a good selection in pregnancy (and for most patients overall).
• Benzodiazepines also appear to be fairly safe (e.g., clonazepam).

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cerebral edema in pregnancy

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• Pregnant women generally have no baseline brain atrophy, which increases the risk of elevated intracranial pressure and/or herniation (because there is no extra space to accommodate brain swelling).
• Osmotic agents appear to carry significant risk:
  • Mannitol may reduce the uterine volume, reduce amniotic fluid volume, and cause fetal hypoxemia and acid-base disturbances.(33896537)
  • Hypertonic saline is poorly studied in pregnancy.  It is a known abortifacient in the first trimester.(34177249)
  • Osmotic agents should be used only if absolutely essential (e.g., in the context of active herniation as a bridge to decompressive surgery).
• Pregnant patients normally have a baseline respiratory alkalosis.  Thus, an intubated pregnant patient should generally be ventilated to target a PaCO2 of ~30-32 mm (regardless of intracranial pressure considerations).(32736751)
• Decompressive craniectomy should be considered earlier than in other patient populations, with preemptive involvement of neurosurgery.(34177249)  
• Normally, labor may cause intracranial pressure to increase as high as 70 cm water.  This may be dangerous for some patients, prompting considerations for vacuum delivery or C-section.(32736751)

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myasthenia gravis in pregnancy

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basics

• Myasthenia exacerbations commonly occur, often in the first trimester and postpartum period. (Louis 2021)  However, among women with myasthenia gravis, the risk of requiring intubation during pregnancy is estimated to be only 0.1%-0.2% (35133311)
• General information on myasthenia gravis is located here: 📖
  • ⚠️ In particular, the list of medications to avoid in myasthenia should be considered: 📖

treatments for myasthenia gravis

• Steroid is reasonably safe in pregnancy and should be utilized for treatment of myasthenia similarly to nonpregnant patients.  However, abrupt initiation of higher doses of steroid may cause a transient exacerbation of myasthenia.  This risk should be considered if steroids are rapidly dose-escalated to induce fetal lung maturity, or for other critical care indications.(30730343)
• Pyridostigmine is safe in pregnancy.  The dose may need to be increased due to increased renal clearance and increased volume of distribution.  However, intravenous pyridostigmine might ideally be avoided prior to labor, as this may induce uterine contractions.(34177249)
• Plasma exchange and IVIG may be used in pregnant women.  However, plasmapheresis causes hormonal shifts that could cause premature labor, so it should be reserved for myasthenic crises.(26600443)  IVIG might be a preferred therapy.(Louis 2021)  More on IVIG vs. plasma exchange here: 📖

myasthenia gravis plus preeclampsia

• Use of magnesium is controversial, since it is frontline therapy for preeclampsia yet it could theoretically increase the risk of myasthenic crisis (there is a paucity of high-quality data on the topic).  Preeclampsia is a leading cause of maternal mortality, so undertreatment of preeclampsia could be quite dangerous.  Ultimately, judgement is required regarding any individual woman's risks from myasthenia versus eclampsia.
• Magnesium may be used with caution and careful observation.(33896537, 30730343) Given controversy regarding the optimal dose of magnesium in preeclampsia, lower doses may be preferable (e.g., 1 g/hr rather than 2 g/hr).📖  Monitoring the magnesium levels might also be considered to improve safety (noting that magnesium itself is not dangerous, but rather marked hypermagnesemia is dangerous).  If toxicity due to hypermagnesemia occurs, this could be managed with IV calcium and discontinuation of the magnesium infusion.  Levetiracetam is safe in pregnancy, so this is another option for seizure management (which might conceivably be combined with a reduced dose of magnesium).
• Beta-blockers are contraindicated in myasthenia gravis.📖  Other agents may be preferable for blood pressure control.

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metastatic choriocarcinoma

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• Choriocarcinoma may occur during pregnancy, with metastasis commonly occurring to the lungs and brain.
• Brain metastases may cause hemorrhage, invasion of cerebral blood vessels, and mass effect.(33896537)
• Choriocarcinoma is extremely sensitive to chemotherapy, with very high cure rates (even despite metastatic disease).

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ventriculoperitoneal shunt malfunction

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• Up to half of ventriculoperitoneal shunts may malfunction during pregnancy, usually during the third trimester.  This may result from elevated intraabdominal pressure, or tissue shifts caused by pregnancy.(32736751)
• Shunt malfunction may manifest with features of elevated intracranial pressure (e.g., headache, nausea/vomiting, confusion, lethargy, abducens nerve palsy).
• CT or MRI may demonstrate worsening hydrocephalus when compared to prior studies.

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podcast

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• A broad laboratory panel is useful for any pregnant woman being admitted to ICU, to avoid missing obscure disorders (e.g., unexpected hepatic failure).
• Fear of radiation exposure should not dissuade the emergent use of CT scanning if this is indicated.

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