Review of Stroke in Pregnancy

January 2020 TOG

Introduction

• Stroke is neurological deficit due to acute focal injury of CNS because of vascular cause which includes cerebral infarction, CVT, ICH and SAH
• Second leading cause of death
• The leading cause of adult disability
• Risk of stroke is 1:6 people
• Not a disease of old age anymore as young are also being affected these days
• Incidence in pregnancy → 30 per 100000 pregnancies ( 3x than in non pregnant aged 15-44yrs)
• 90% occur in peripartum or 6wks after delivery
• Stroke in antenatal period → 1.5 per 100000 deliveries (UKOSS)
• Overall Risk of stroke Recurrence
• 0 –1.8% in a subsequent pregnancy
• 0.5% outside of pregnancy
• with concurrent thrombophilia risk is up to 20%
Independent risk factors

1. Age >35 yrs
2. Migraine
3. GDM
4. PET/Eclampsia
5. Pre-existing HTN
6. Overall case fatality in pregnancy 8-20%
   o Haemorrhagic 14%
   o Ischemic 3.4%
   • Residual disability: Haemorrhagic 50% Ischemic 33%
   • ICH single greatest cause of maternal death from stroke
   • Most stroke in general population is ischemic (80-85%) but in pregnancy same contribution due to ischemia, haemorrhage & VTE
   • Risk of CVT ↑ in pregnancy because of physiological upregulation of clotting factors
   • Pregnancy-specific conditions which further ↑ hyper coagulation include OHSS, Hyperemesis Gravidarum & PET
   • Conditions(prothrombic) which↑risk of ischemic stroke are APS, SCD, TTP, HUS, mechanical heart valves & cardiomyopathies
   • Hypertensive diseases including PET & eclampsia ↑the risk of hemorrhagic or ischemic stroke & could be associated with posterior reversible encephalopathy syndrome (PRES) / reversible cerebral vasoconstriction syndrome
   • Amniotic fluid embolism is also associated with stroke
   Clinical presentation, symptoms and signs of stroke
   • Stroke is a clinical syndrome with rapidly developing symptoms, with signs of focal cerebral loss of function & no cause other than of a vascular origin
   • Signs and symptoms relate to affected brain areas
   • Good history from patient/witness is vital in identifying timing & sudden nature of symptom onset
   • Onset of stroke is typically sudden, with focal symptoms & clinical deficits conforming to a vascular territory
   • Symptoms include:
   • Unilateral Numbness/weakness of face, arm or leg; dysphasia; hemianopia & cerebellar features (dysarthria & ataxia)
   • Non focal symptoms(less likely) like generalised weakness +/- sensory disturbance, light-headedness, brief loss of consciousness, urinary or faecal incontinence, confusion & tinnitus
   • CVT may have variable clinical presentation, with only 40% presenting with typical stroke symptoms & signs (often associated with headache, drowsiness or confusion)
   • Subarachnoid haemorrhage is a consequence of bleeding with hypertension (rather than being a cause)
   • Hypertension + relative bradycardia → suspicion of intracranial bleed rather than a stroke. If severe could be associated with ↑ intracranial pressure
   • Headache, nausea, vomiting & depressed level of consciousness are more common in haemorrhagic strokes
   • Systemic BP higher in ICH than in acute ischemic stroke(AIS)
   • Fits may follow stroke
   • Rule of thumb: most new-onset fits after 20 wks of gestation & up to 2 wks postpartum are due to eclampsia unless proven otherwise
   • Focal neurological deficits are NOT typical of eclampsia, but visual symptoms are
   • Persistent focal neurological symptoms + signs or visual symptoms despite BP control MUST have imaging
   Specific questions to ask when taking a history
   • Where were you when you experienced symptoms of stroke?
   • What were you doing at that time?
   • What did you first notice was wrong?
   • When were you last free of symptoms?
   • Then what happened?
   The FAST campaign, outlining how to recognise symptoms of stroke
   • F – Face drooping A – Arm weakness S – Speech difficulty T – Time to call
   Investigations and management of stroke

Scores to be recorded on NIHSS and modified Rankin Scale (Click Here for Tables)

Imaging
• Imaging to be done promptly in pregnancy
• All patients with suspected AID should have brain imaging on hospital arrival
• Non-contrast CT will give information to make decision about acute management (e.g I/V thrombolysis)
• ICH is contraindication to thrombolysis. Mx directed to secure haemostasis & correction of coagulopathy with surgery if needed
• CT angiogram to be done for potential candidates of mechanical thrombectomy for evaluation of large vessel occlusion
• better in detecting high degrees of cerebral arterial stenosis
• safe in pregnancy with less radiation exposure than CT perfusion.
• Theoretical risk of fetal thyroid suppression so neonatal thyroid function test to be monitored in initial 2 weeks of life
• CT perfusion: better specificity in detecting infarction & ischemia of brain tissue
• CT most appropriate tool for initial rapid diagnosis as its access is easier
• Fetal radiation <0.1 Gy not associated with increased adverse risk
• Combination of CT perfusion and CT angiogram → Most accurate assessment of site of occlusion, infant core, salvageable brain tissue & collateral circulation
• Preferred first line imagining in pregnancy: MRI
• MRI further distinguishes between stroke subtypes & vascular imaging
• Potential hazards: theoretical biological damage, tissue heating & potential damage to fetal ear
• No harmful short or long term effects on fetus at T1.5 or less
• On MRI white matter lesions are
• hyper intense on T2
• hypo intense on T1
• freely diffused on diffusion-weighted imaging
• Gadolinium chelate may be used to enhance MRI studies.

Only 0.01% remains present ion fetus after 4 hrs and only traces remain after 24 hrs.

Must be used with extreme caution and after well-documented informed consent
Investigations for underlying causes of stroke

Management of stroke “Time is brain” approach to be adopted

Intravenous thrombolysis

• Recombinant tissue plasminogen activator (rt-PA) significantly improves overall outcome of stroke if given within 4.5 hrs of onset
• Risk of haemorrhagic transformation → 2-6%
• Does not cross placenta but there is theoretical risk of placental bleeding & IUFD
• Earlier the treatment, bigger the proportional benefit

Contraindications to thrombolysis
Absolute Relative

1. Intracerebral haemorrhage
2. Suspected subarachnoid haemorrhage, even if normal computed tomography (CT)
3. Neurosurgery, head trauma within the last 3 months
4. Systolic blood pressure >185 mmHg, diastolic blood pressure >105 mmHg
5. History of intracerebral haemorrhage
6. Known intracerebral arteriovenous malformation, neoplasm or aneurysm
7. Active internal bleeding
8. Suspected/confirmed endocarditis
9. Known bleeding diathesis
10. Platelets <100 000
11. Heparin within 48 hours
12. Current use of warfarin with international normalised ratio (INR) >1.7 s
13. Direct thrombin inhibitors or factor Xa inhibitors
14. Blood glucose <2.8 or >22.2 mmol/L, with resolution of symptoms when corrected 1. Age >80 years
15. National Institutes of Health Stroke Scale >25 and coma
16. Multilobar infarction on CT
17. Previous stroke within the last 3 months
18. Diabetes mellitus and previous stroke
19. Minor or rapidly improving stroke
20. Major surgery or serious non-head trauma within 14 days
21. Gastrointestinal or urinary tract haemorrhage within 21 days
22. Seizure at stroke onset
23. Recent arterial puncture at non-compressible site
24. Recent lumbar puncture
25. Post myocardial infarction pericarditis
26. Pregnancy

Post‐stroke thrombolysis care

1. 24 hours of bedrest (may not be essential if very stable)
2. Maintain O 2 saturations above 95%
3. Maintain normal temperature; use paracetamol if >37.5°C
4. Maintain blood glucose <10 mmol/l
5. Deep vein thrombosis prophylaxis with intermittent pneumatic compression devices (as per the CLOTS-3 study)
6. No arterial lines, nasogastric tubes or central lines for 24 hours
7. No urinary catheter until at least 1 hour after infusion ends
8. Avoid suctioning and careful mouth care
9. No aspirin, clopidogrel, dipyridamole or anticoagulants for 24 hours
10. Repeat computed tomography in 24–36 hours
11. Hydration and nutrition
12. Fall risk assessment and prevention
13. Stop rt-PA if neurological deterioration of 2 points on Glasgow eye/motor scale
14. Observe for signs of systemic bleeding – stop rt-PA
15. Blood pressure – stop rt-PA if systolic blood pressure <100 or >180 mmHg & diastolic blood pressure >105 mmHg if sustained for more than 5 minutes
16. Observe for signs of anaphylaxis – stop rt-PA

Mechanical thrombectomy
• Mechanical thrombectomy with stent retriever devices superior to I/V RFT-PA alone. Benefits up to 6 hours
• All eligible patients should be considered for clot retrieval & urgently referred. It can be performed up to 24 hours stroke onset.
• Outcomes for disability at 90 days are better with thrombectomy plus standard care than with standard care alone
• Thrombectomy can only be done in specialized centers & appropriate in 10% cases of AIS

Management of Intracerebral Haemorrhage (ICH)
• Haemostasis, correction of coagulopathy & hyper/hypoglycemia
• BP control & VTE prophylaxis
• Correct coagulopathy & thrombocytopenia
• Use antiepileptic medication to treat seizures
• Consider surgical decompression in cerebellar haemorrhage with deteriorating neurological function

Management of Cerebral Venous Thrombosis (CVT)
• Anticoagulation with LMWH or unfractionated heparin
• If anticoagulation contraindicated or patient does not respond then thrombolysis or thrombectomy can be considered
• Patients with ↑ intracranial pressure can be treated with I/V mannitol & considered for decompressive craniectomy
Management of pre-eclampsia/eclampsia and posterior reversible encephalopathy syndrome
• MgSO4 is well documented in treatment & prevention of eclampsia.

It increases seizure threshold & decreases neuroimflammation
• PRES is associated with PET/eclampsia, HTN, infection/sepsis, shock, autoimmune disease, drugs, chemotherapy & massive transfusion
• Optimise BP, Remove/ Treat suspected causative factors.
• Deliver the baby in case of PET/Eclampsia.
• Most cases resolve on it own within days to weeks

Stroke Unit Care
• Multidisciplinary unit with focused nursing care, specialist medical treatment with protocols, coordination of rehabilitation services & patient education.
• Patients more likely to be alive, independent & living at home 1 yr after stroke.
• It leads to separation of mother and baby & may have effect on bonding/feeding

Secondary prevention strategies

• Recurrent stroke → 25-30% of all strokes
• BP management is one of the key elements of secondary prevention & should be aggressive
• Gradual, sustained lowering of BP is recommended for ALL stroke patients
• Increased maternal mortality with systolic BP >160 & diastolic >100 mmHg mainly due to ICH
• Recommended to give aspirin in AIS within 24-48 hrs of onset.

If patient receiving thrombolysis, aspirin is delayed until 24 hrs later (when ICH excluded)
• In minor stroke or TIA dual anti platelates therapy (aspirin & clopidogrel) started within 24 hrs & continued for 21 days may be beneficial for early secondary stroke prevention.

To be used cautiously as it has higher risk of major haemorrhage at 90 days vs patients on aspirin alone.
• Clopidogrel is category B drug,
• treatment should not be withheld due to pregnancy
• should be stopped 7-10 days before schedule delivery
• If patient goes into spontaneous labour, do not use neuroaxial anaesthesia
• Patients with AIS/atrial fibrillation, initiate oral anticoagulation within 4-14 days of neurological symptoms onset
• High-intensity statin therapy should be initiated or continued as a first-line therapy in all with clinical atherosclerotic cardiovascular disease, unless contraindicated
• Smoking cessation is an important part of secondary prevention
• The incidence of patent foramen ovale (PFO) in the general population is approximately 20%

Mode of delivery
• Decision requires multidisciplinary input & should be individualised

Postpartum management and contraception
• Postpartum is the highest risk period for VTE & Stroke.
• Continue anticoagulation for atleast 6 weeks postpartum.
• MDT approach
• Factor V Leiden heterozygosity & persistent lupus anticoagulant is associated with increased risks of transient ischaemic attacks, amaurosis fugax & ischaemic stroke.
• Complete thrombophillia screen at 6 weeks postnatal
• Warfarin, LMWH & Aspirin safe in breastfeeding
• Combined Hormonal Contraception is contraindicated
• Use non-hormonal contraception
• Progesterone only can be considered
Pre-conceptual care
• Individualised care in women with prior stroke
• No specific secondary prevention strategy
• Closely monitor future pregnancies as high risk of recurrence

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