Coma In Pregnancy

Coma In Pregnancy

Dr Sankalp MohanSenior Resident NeurologyGMC Kota

Pregnant women may go into coma for the same reasons that face the general population, but also encounter conditions unique to or more common in this state - Gestational hypertension, eclampsia, and HELLP- Pregnancy related organ failures including acute renal, hepatic, or pulmonary failure- Vascular risks include cerebral venous sinus thrombosis and pituitary apoplexy

STROKE IN PREGNANCY Ischemic Strokesincidence of 3.5 ischemic strokes per 100 000 populationit is recognized that there is an increased risk of stroke associated with pregnancy recent studies show similar incidence- considering stroke in the young as a broader group, strokes related to pregnancy account for 12% to 35% of eventsBased on the available evidence, the highest risk periods appear to be the delivery period and up to 2 weeks postpartum.

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Etiology Etiology similar to other causes of young stroke- Cardioembolic common Physiologic and hemodynamic changes that occur --state of relative hypercoaguability, Increased cardiac burden, and altered vascular tonePreeclampsia,, is associated with a 4-fold increase in stroke during pregnancyParadoxical embolism related to the presence of a patent foramen ovale (PFO) may be facilitated by both the coagulation profile changesPeripartum Cardiomyopathy , Post partum cerebral angiopathy

acute onset of focal neurological changesheadache and altered consciousnessSiezures

Diagnosisinitial study with a noncontrast head computerized tomography (CT) with appropriate fetal shielding or an magnetic resonance imaging (MRI) of the brain

Transthoracic or transesophageal echocardiogram to evaluate for PFO and the possible presence of an intracardiac thrombus hypercoaguability panel is often performed - results will need to be repeated several weeks following deliveryGenetic testing for factor V Leiden and prothrombin gene mutation would not be altered by pregnancy

Treatment TPA - pregnant patients were excluded from tPA clinical trials and there has been no systematic studyConcerns regarding the risks of tPA on the pregnant patient and fetus (eg, uterine hemorrhage, placental abruption, abortion, preterm delivery) have been raisedthat maternal mortality (1%), fetal loss (6%), and preterm delivery (6%) are all lowLow-dose aspirin for secondary prevention is felt to be safe during pregnancy

unfractionated or low-molecular weight heparin as these do not cross the placenta and confer no risk of teratogenicity or fetal hemorrhage

Antiphospholipid Antibody SyndromeRecurrent arterial and venous thromboses and can cause fetal deathsimilarities to preeclampsia-eclampsia, with endothelial damage, platelet activation, and thomboxane-mediated vasoconstrictioninhibition of protein C-protein S and antithrombin III activity

Focal problems include cerebral infarction from thrombotic and venous occlusionAntibodies contribute to the pathogenesis, and include the lupus anticoagulant antibody, anticardiolipin antibody, and anti-B2 glycoprotein

CARDIAC CAUSES OF STROKE IN PREGNANCY Peripartum Cardiomyopathy-defined as an unexplained cardiac failure occurring during the last month of pregnancy to the first sixth postpartum month.viral and autoimmune causes of cardiomyopathy have been invokedComa may occur from global cerebral hypoperfusion or by strokes

Heart Valve AbnormalitiesProsthetic heart valves or chronic atrial fibrillation may induce strokeIn normal childbirth and with Valsalva maneuvers, right atrial pressure rises and the foramen ovale may open, enabling pelvic and peripheral vein emboli to pass to the lung

Amniotic Fluid EmbolismAFE occurs when amniotic fluid enters uterine veins and is forced into the maternal circulation, causing hemodynamic collapse, disseminated intravascular coagulopathy (DIC),focal cerebral hypoperfusion, thrombosis or hemorrhage,

Hemorrhagic strokeoccurs primarily in late pregnancy and in the puerperiumintracerebral hemorrhage has a higher maternal mortality rate -5% to 12% of overall maternal mortality during pregnancyprimarily associated with preeclampsia / eclampsia, arteriovenous malformations, and cerebral aneurysm rupturePathogenesis - increased blood volume, rising blood pressure, and changes in vascular tone. physical stress of labor and delivery may contribute to rupture risk

initial evaluation should include a noncontrast head CT which will identify a subarachnoid (often aneurysmal) or lobar (often AVM) hemorrhageangiographic imaging in an attempt to identify the source of the hemorrhage

Treatment patients with known aneurysms and AVMs are often delivered by scheduled C-sectionan aneurysm is identified during pregnancy repair is usually undertaken with neurosurgical clipping or endovascular coiling as this has been shown to reduce both maternal and fetal mortality

Cerebral Venous ThrombosisCVT represents 0.5% to 1% of all strokes.Risk factors are usually divided into acquired risks (eg, surgery, trauma, pregnancy, puerperium, antiphospholipid syndrome, cancer, exogenous hormones) and genetic risks (inherited thrombophilia).Pregnancy and Puerperium-Most pregnancy-related CVT occurs in the third trimester or puerperium.

PathophysiologyPregnancy induces several prothrombotic changes in the coagulation system fibrinogen activation with increased platelet adhesiveness Hypercoagulability worsens after delivery as a result of volume depletionAdditional risk factors include infection and instrumental delivery or cesarean sectionIncreasing maternal age, as well as in the presence of hypertension, infections, and excessive vomiting in pregnancy

Clinical Diagnosis of CVT

headache in 82%, papilledema in 56%, focal deficits in 42%, seizures in 39%coma in 31%.

location of the thrombosisThe superior sagittal sinus is most commonly -headache, increased ICT, and papilledemamotor deficit, sometimes with seizures

DIPLOPIA due to 6th nerve , focal hemiparesis aphasia18

lateral sinus thromboses, symptoms related to an underlying condition (middle ear infection )16% of patients with CVT have thrombosis of the deep cerebral venous system - Thalamic or basal ganglial infarction ,rapid deterioration bilateral involvement -bilateral thalamic involvement - Coma ; paraparesis, may also be present due to sagittal sinus thrombosisCVT often present with slowly progressive symptoms

Coma in CVT raised ICT or deep venous thrombosis19

InvestigationsRoutine blood studies consisting of a complete blood count, chemistry panel, prothrombin time, and activated partial thromboplastin time should be performed

TreatmentTreatment of CVT in the nonpregnant population generally involves anticoagulation with warfarinunfractionated heparin or low-molecular weight heparin can be utilized in pregnancy either as a bridge to warfarin therapy or as a stand-alone treatment

Reversible Cerebral Vasoconstriction Syndrome

encompasses a variety of syndromes including postpartum angiopathy and puerperal vasospasmgroup of disorders linked by prolonged but reversible vasoconstriction of the cerebral arteriesClinical settings including the postpartum state, migraine, hypertensive encephalopathy, and the use of vasoactive medications/drugsevere, acute-onset headaches hunderclapIschemic strokeand/orhemorrhage associated with reperfusion may occur

characteristic imaging features associated with the syndrome which often include focal regions of symmetric edema in the posterior brain parenchyma

RCVS

ChoriocarcinomaMetastatic choriocarcinoma rarely causes SAH, ICH, or subdural hemorrhageTrophoblastic tissue may invade blood vessels and induce aneurysmal dilatation, which may cause rupture

EclampsiaPREECLAMPSIA - New onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman Criteria for the diagnosis of preeclampsiaSBP 140 mmHg OrDBP 90 mmHgAnd Proteinuria 0.3 grams in a 24-hour urine specimen EclampsiaOccurrence of one or more generalized convulsionsand/or coma in the setting of preeclampsia and in the absence of other neurologic conditions.Many patients have an incomplete clinical triad but a seizure or coma define eclampsia

Eclampsia may occur without previous setting of preclampsiaBp above 140/90 without proteinuria beyond 20 weeks Gestational hypertension26

Eclampsia occurs in 0.05% to 0.20% of pregnanciesEclamptic seizure occurs in - 3% of severely preeclamptic women not receiving anti-seizure prophylaxis

Risk Factors

Preeclampsia in a previous pregnancyAge >40 years or 160 mmHgDiastolic bp>110mHgProteinuria> 5g per 24 hoursCerebral or visual disturbances: headache, tinnitus, Oliguria< 500ml per 24 hours, creatinine>1.2mg/dlEpigastric painPulmonary oedemaHeamolysis, elevated liver enzymes and low plataletsyndrome= HELLP syndromeFetal criteria-IUGR, oligohydro, fetal death

Impending Eclampsia

Symptoms:HeadacheVisual disturbanceEpigastricpainNauseaRestlessnessSwellingPoor urine output

Stroke with EclampsiaMost common causes of both ischemic and hemorrhagic stroke in pregnancy.The most frequent cerebrovascular disturbance associated with eclampsia is a reversible encephalopathy. Preeclampsia/eclampsiacommonly associated with ischemic stroke of arterial origin [36 percent]) , Intracerebralhemorrhage [55 percent])

PrognosisPostpartum eclampsia has a worse prognosis, often with adult respiratory distress syndrome (ARDS) and DICNeurological complications more in postpartumPreclampsia increases risk of stroke over 42 days postpartum

Management Investigations- Platelet count and morphology, CBCPT, aPTT Uric acid, creatinin, electrolytes for renal functionSerum uric acid useful early and for progressionHepatic enzymes (AST,ALT,GGT)& bilirubin

Imaging

Cerebral imaging is not necessary for the diagnosis and management of most women with eclampsia. Cerebral imaging findings in eclampsiaare similar to those found in patients with hypertensive encephalopathy

Cerebral imaging is indicated :-focal neurologic deficitsprolonged comaatypical presentation for eclampsia:onset before 20 weeks of gestation ormore than 48 hours after deliveryeclampsia refractory to adequate mgso4 therapy

Treatment Management of siezures Magnesium sulphate: -anticonvulsant of choice Action by: antagonism of calcium and hence decreased systemic and cerebral vasospasm Increase release of PGI2 by vascular endotheliumMgso4 52% lower occurrence of siezure compared to Diazepam , 67% compared to phenytion

Therapeutic level 4-7 mEq/l ; must monitor for toxicityreduce dose in renal failure MANAGEMENT OF HYPERTENSION Nifedepine,Hydralazine ,Labetalol

Posterior Reversible Encephalopathy Syndrome

Is a clinical radiologic syndrome of heterogeneous etiologies that are grouped together because of similar findings on neuroimaging studies May occur in the setting of preeclampsia due to impaired cerebral autoregulation from endothelial damage

most common clinical manifestations of PRES include headaches, confusion, seizures, and visual changes.Confusion is common and may progress to more significant degrees of altered awarenessseizures may start focally but often generalizemore severe cases can result in lasting neurological morbidity or mortality due to ischemic stroke or hemorrhage

Findings in PRES

treatment of PRES in the pregnant patient mirrors that of eclampsiaMagnesium sulfate is often utilized for seizure controlAs with eclampsia, hypertension management is generally achieved with hydralazine or labetolol

SEIZURES AND STATUS EPILEPTICUSPregnancy may increase seizure frequency in women with epilepsy, but produces no effect in most women; some have fewer seizuresPregnancy decreases the total blood levels of most antiepileptic drugs (AEDs) by 50%Free valproate levels may increase. Lamotrigine levels may decrease

Frequent causes of SE are a low level of AEDs, new strokes, infections, abscesses, and vascular malformationsManagement is directed at seizure control and investigation of possible underlying causes

METABOLIC CAUSES OF COMA Glucose Dysregulation-Diabetes causing high or low blood sugar that can lead to comamorning sickness, may cause the mother to avoid glucose-lowering medication and facilitate hyperglycemia.Vomiting with dehydration can cause hypernatremia Wernicke Encephalopathyconfusion, eye movement disorders and nystagmus, ataxia, and rarely, comaHyperemesis gravidarum may cause Wernicke encephalopathy by depleting the body thiamine storesTreatment may require daily parenteral thiamine repletion for 7 to 10 days

Acute Intermittent Porphyria-caused by an autosomal dominant inherited abnormality of heme biosynthesis with toxic accumulation of aminolevulinic acid and porphobilinogencan be precipitated in women during menarche, perimenstrually, and in pregnancyAcute axonal polyneuropathyautonomic dysfunction with tachycardia and constipation, cognitive and behavioral abnormalities, and psychosis, occasionally with coma.Seizures may be difficult to control because of the porphyrinogenic nature of most AEDsbenzodiazepines. gabapentin, levetiracetam, or vigabatrin

ENDOCRINE DISTURBANCES IN PREGNANCYPituitary apoplexy can arise from increased vascularity, and enlargement of the pituitary result in antepartum infarction or hemorrhage Acute pituitary apoplexy emergency with high mortality, often fromcompression of the hypothalamusConsciousness is impaired and there is the danger of acute adrenal failure and further hypotension

Treatment is aimed at acute replacement of corticosteroids intravenously. Surgery to decompress the hypothalamus or optic nerve

Sheehan Syndromeanterior pituitary necrosis after hypovolemia and hypotension in severe maternal blood loss pituitary, because of its pregnancy-associated hyperplasia and increased vascularity, is particularly vulnerable to hypovolemia and hypotensionTreatment replacement of hormones

INFECTIONSmild immunosuppression in pregnancy associated with alterations in circulating maternal steroidssystemic infections and septicemia, but rarely coma.

INFECTIONSHerpes simplex virus encephalitis in pregnancy

ORGAN FAILURE OCCASIONALLY LEADING TO COMA

RENAL FAILUREARF may be caused by hemorrhagic or septic shock, or severe preeclampsia.HELLP may lead to a decrease in glomerular filtration and renal failure, occasionally with acute tubular necrosis- usually resolvesDIC causes ARFOther -malignant hypertension, infections, scleroderma, vasculitis, microangiopathichemolytic anemia transplant rejection, hemolytic uremic syndrome, malignancies, or drug toxicity.

Acute Liver Failure-prepartum or postpartum with eclampsia, HELLP syndrome, or acute viral hepatitisAcute fatty liver and HELLP syndrome occur most frequently in the third trimester itching, diarrhea, and jaundice COMA- patients with encephalopathy, coagulopathy, hypoglycemia

Acute Fatty liver of pregnancy1 in 7000 to 16,000 pregnanciesMaternal mortality is almost 20%usually is seen in the third trimester of pregnancy, and presents with hepatic failure, microvesicular fatty infiltration of the liver, and encephalopathyNausea and vomiting (75%), jaundice, or epigastric pain. There may be DIC, acute tubular necrosis, and pulmonary edemaTreatment is with supportive measuresOn occasion, liver transplantation is recommended

PULMONARY DISEASE AND FAILURE IN PREGNANCYAcute respiratory failure and ARDS, and all of the pulmonary disorders may cause coma from hypoxia.Acute respiratory failure in pregnancy accounts for more than 30% of maternal deathsthromboembolism, AFE, venous air embolism, or ARDS

Aspiration pneumonia may arise during decreased consciousness in labor and delivery, an increase in intragastric pressure by compression by the pregnant uterus, and delayed gastric emptying, all contributing to significant of maternal morbidity and mortality

Venous Air Embolism - predominantly iatrogenic complicationabortion, delivery, labor, and other interventions, and is caused by air entry into the subplacental venous sinusesrisk is higher in pregnant women, who may have a tear in their placentae.complications have been reported with as little as 20 mL of airmore than 5 mL/kg of air displaced into the intravenous space is required for significant injury (shock or cardiac arrest)

Air travels to the heart and prevents blood flow to the lungs, frequently causing a blood-air interface, with microemboli, platelet injury, and inflammatory white cell response leading to ARDSclinical features include shortness of breath, tachypnea and tachycardia, hypotension, and sweating.. sitting position, gas will travel internal jugular vein to the cerebral circulation, leading to neurologic symptoms. In a recumbent position, gas proceeds into the right ventricle and pulmonary circulationclinical picture similar to that of pulmonary embolism, with hypoxia, decreased PCO2levels pulmonary veins.

Most venous air emboli go unrecognized because their presentations are protean and mimic other cardiac, pulmonary, and neurologic dysfunctions58

Lab tests not sensitive or specificCXRTransesophageal echocardiography (TEE) has the highest sensitivity for detecting the presence of air in the right ventricular outflow tractCT scans can detect air emboli in the central venous systemManagement includes identification of the source of air, prevention of further air entry hemodynamic support.

Cpr hyperbaric oxygen therapy , Direct removal of air from the venous circulation by aspiration from a central venous catheter in the right atrium59

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ReferencesComa in the Pregnant Patient- NEUROLOGY CLINICS11/2011; 29(4):973-94.Stroke and Pregnancy - Stroke.2000;31:2948-2951Acute Neurological Issues in Pregnancy and the Peripartum - Neurohospitalist. 2011 Apr; 1(2): 104116.Bradley's Neurology in Clinical Practice 6 e- Neurologic complications of pregnancywww.medscape.com