Eclampsia – neurological aspects

1. DR. SUMIT KAMBLE
SENIOR RESIDENT
DEPT. OF NEUROLOGY
GMC, KOTA

2. PREECLAMPSIA
New onset of hypertension and proteinuriaafter
20 weeks of gestation in a previously
normotensivewoman
Criteria for the diagnosis of preeclampsia
Systolic blood pressure ≥140 mmHg
Or
Diastolic blood pressure ≥90 mmHg
And
Proteinuria≥0.3 grams in a 24- hour urine
specimen
Sibaib et al. Preeclampsia. Lancet.2005;365:785-799

3. Eclampsia–
Occurrence of one or more generalized
convulsionsand/orcoma in the setting of
preeclampsia and in the absence of other
neurologic conditions.
Sibaib et al. ACOG. Diagnosis, preventionand mm of eclampsia;.2005;402- 410

4. Eclampticseizureoccursin2-3%of
severelypreeclampticwomennotreceiving
anti-seizureprophylaxis;
Incidenceofeclampsiaindeveloping
countriesvarieswidely:from6to157cases
per10,000deliveries

5. Approximately one maternal death due to
eclampsiaper 100,000 live births
case-fatality rate of 6.4 deaths per 10,000 cases
Geographic variation in the incidence of hypertension in pregnancy. World Health
Organization International Collaborative Study of Hypertensive Disorders of Pregnancy.
Am J ObstetGynecol1988; 158:80.
LubarskySL, Barton JR, Friedman SA, et al. Late postpartum eclampsiarevisited. Obstet
Gynecol1994; 83:502

6. Nulliparity
Preeclampsia in a previous pregnancy
Age >40 years or <18 years
Family history of preeclampsia
Chronic hypertension
Chronic renal disease
Antiphospholipidantibody syndrome or inherited
thrombophilia
Vascular or connective tissue disease
Diabetes mellitus (pregestationaland gestational)
MultifetalgestationHigh
body mass index

7. Black race
Hydropsfetalis
Unexplained fetal growth restriction
Fetal growth restriction,
abruptioplacentae, or fetal demise in a previous
pregnancy
Prolonged interpregnancyinterval
Partner related factors (new partner,limtedsperm
exposure [eg,previous use of barrier contraception])
Hydatidiformmole
Susceptibility genes

8. Symptoms:
•Headache
•Visual disturbance
•Epigastricpain
•Nausea
•Restlessness
•Swelling
•Poor urine output
signs:
•Agitation
•Hyperreflexia
•Facial &peripheral
oedema
•Rtupper quadrant
tendernes

9. Features of pre-eclampsiaplus one the
following:
–Systolic bp>160 mmHg
–Diastolic bp>110mHg
–Proteinuria> 5g per 24 hours
–Cerebral or visual disturbances: headache, tinnitus,
–Oliguria< 500ml per 24 hours, creatinine>1.2mg/dl
–Epigastricpain
–Pulmonary oedema
–Heamolysis, elevated liver enzymes and low plataletsyndrome=
HELLP syndrome
–Fetal criteria-IUGR, oligohydro, fetal death

ACOG,PracticeBull.2002

10. •Cerebrovascularaccidents
•Hypertensive encephalopathy
•Seizure disorder
•Previously undiagnosed brain tumors
•Metastatic gestational trophoblasticdisease
•Metabolic diseases- hyponatremia, hypoglysemia
•Reversible posterior leukoencephalopathy
syndrome
•Cerebral vasculitis

SibaiE. Diagnosisand management of eclampsia. ACOG 2005

11. Headache- temporal, frontal, occipital, or
diffuse
Generalized hyperreflexia; sustained ankle
clonusmay be present.
Visual symptoms -include blurred vision,
flashing lights (photopsia ), and scotomata.
Diplopiaor amaurosis fugaxmay also occur.
Cortical blindness is rare .

12. Blindness related to retinal pathology, optic
nerve damage, retinal artery spasm, and
retinal ischemia, may be permanent
Seizures
Posterior reversible leukoencephalopathy
syndrome (PRES)

Stroke leading to death or disability is the most serious complication

13. Cerebral overregulation results in vasospasm
of cerebral arteries, underperfusionof the
brain, localized ischemia/infarction,and
cytotoxic(intracellular) edema.
Loss of autoregulationof cerebral blood flow
(ie, hypertensive encephalopathy) results in
hyperperfusion, endothelial damage, and
vasogenic(extracellular) edema.
MorrissMC, Twickler DM, Hatab MR, et al. Cerebral blood flow and cranial
magnetic resonance imaging in eclampsiaand severe preeclampsia. Obstet
Gynecol1997; 89:56

14. General principles-
The immediate issues in caring for an
eclampticwoman include:
1.Prevention of maternal hypoxia and trauma
2.Management of severe hypertension, if present
3.Prevention of recurrent seizures
4.Evaluation for prompt delivery.

15. Maternal assessment should include:–
History and examination: BP, weight gain,
edema, sensorium
–Serial or continuous blood pressure
monitoring
–Urinanalysisfor proteinuria
–quantification for degree of severity

16. –Blood test include
•Platelet count and morphology, CBC
•Haemocoagulationsystem: PT, aPTT
•Uric acid, creatinin, electrolytes for renal
function
•Serum uric acid –useful early and for
progression
•Hepatic enzymes (AST,ALT,GGT)& bilirubin
–Fluid balance –urine output, CVP, SP02 etc
–ECG

17. •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.

18. Cerebral imaging is indicated :-
•focal neurologic deficits
•prolonged coma
•atypical presentation for eclampsia:
•onset before 20 weeks of gestation or
•more than 48 hours after delivery
•eclampsiarefractory to adequate mgso4 therapy
SibaiBM. Hypertension and Obstetrics. Churchill Livingstone. 2002

19. •Fetal monitoring:–
-Cardiotocography–for acceleration, loss of
variability or decelerations
–Fetal ultrasound -may be useful for fetal size and
morphology, amniotic fluid volume estimation
–Placental and fetal blood flow measurement of
uterine artery and main fetal Doppler
velocimetry(including diastolic flow)

20. Treatment required when:–
Systolic bp> 160 mm Hg or
Diastolic bp> 110 mm Hg
Hydralazine: agent of choice(5-10mg IV
max30)
–Causes direct arteriolar vasodilation
–Improves renal and uteroplacentalblood flow

21. •Labetalol: causes rapid decrease in arterial
bpwithout compromising uteroplacentalflow
–May cross placenta but fetal complications
rare
–20-40mg every 30min for a max of 220mg
IV

22. Nifedipine: oral 10-20mg every 30min for a
max of 50mg
-causes direct relaxation of arteriolar smooth
muscle
–Maintains uterine perfusion
–Can cause uterine muscle relaxation
–increase risk of post partum haemorrhage–
Relative contra-indication with use of Mg

23. •Sodium nitroprusside: hypertensive
emergencies but should be avoided due to
safety concern
•Nitroglycerin: useful especially when
pulmonary oedemacomplicates situation
WHO recommmendationsfor preventionand treatmentof PEC & EC 2011

24. Reasonable goal is systolic BP of 140 to 155
mmHg and diastolic BP of 90 to 105 mmHg.
In women with extremely severe
hypertension(≥180/120mmHg), a diastolic
goal of 100 to 105 mmHg should be achieved within two to six hours, with the maximum initial (within 10 to 20 minutes) fall in BP not exceeding 25 percent of the presenting value
Vaughan CJ, DelantyN. Hypertensive emergencies. Lancet 2000; 356:411.
LedinghamJG, RajagopalanB. Cerebral complications in the treatment of accelerated
hypertension. Q J Med 1979; 48:25

25. Use of antihypertensive agents to control
mildly elevated blood pressure in the setting
ofpreeclampsia/eclampsia has not been
shown to alter the course of the disease, nor
to diminish perinatalmorbidity or mortality.
SibaiBM. Treatment of hypertension in pregnant women. N EnglJ Med 1996; 335:257.
von DadelszenP, Ornstein MP, Bull SB, et al. Fall in mean arterial pressure and fetal growth
restriction in pregnancy hypertension: a meta- analysis. Lancet 2000; 355:87.
Magee LA, Ornstein MP, von DadelszenP. Fortnightly review: management of hypertension in
pregnancy. BMJ 1999; 318:1332.

26. •Airway protection
•Maintain oxygenation(O2 inhalation via mask)
•Control of seizures– Continued convulsions may
indicate other cerebral pathology– Management
may involve treatment cerebral oedema
•Delivery of fetus when mother is in stable
condition, even in some situation CS is needed
acutely

27. •Magnesium sulphate: -anticonvulsant of choice
–Action by:
•antagonism of calcium and hence decreased
systemic and cerebral vasospasm
•Increase release of PGI2 by vascular endothelium
–Other effects in parturient include:
•Tocolysis
•Decreased cathecholaminerelease
•Mild antihypertensive
•Increases renal and uterine blood flow

28. –Renalyexcreted–so reduce dose in renal
failure
–Therapeutic level 4-7 mEq/l ; must monitor
for toxicity
–Repeated seizures despite therapeutic levels
need to consider other anticonvulasnts.

29. Regimen Loading Dose Maintenance Dose
Pritchard
(Intramuscular)
4gm IV over 3-5 min
f/b 10gm deep IM(5gm
eachbuttock)
5gm IM 4 hourly in
alternate buttock
Zuspanor Sibai
(Intravenous)
4gm IV over 15-20
min.
1-2gm/hrIV infusion
4/2/2015Dutta’s. Hypertensive disorder of pregnancy: 17 29

30. •Hypotension, flushing, slurred speech,
drowsiness, double vision
•Absent reflexes
•Respiratory paralysis
•Conduction (heart) disturbances
•Cardiac arrest–Calcium Gluconate1G slow
push –10 min

31. An additional benefit ofmagnesium
sulfatetherapy is in women expected to have
a preterm delivery within 24 hours have
consistently demonstrated a decreased risk of
cerebral palsy and severe motor dysfunction
in offspring
CrowtherCA, Hiller JE, Doyle LW, et al. Effect of magnesium sulfate given for neuroprotectionbefore
preterm birth: a randomized controlled trial. JAMA 2003; 290:2669.
Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate for the
prevention of cerebral palsy. N EnglJ Med 2008; 359:895 .

32. •Additional bolus of 2 grams of magnesium
sulfate over 15 to 20 minutes, with careful
monitoring for signs of magnesium toxicity.
• Phenytoin: effective in pre- eclampsia
–Central anticonvulsant activity
–No effect on uterine tone, fetal HR or neonatal
tone
•Diazepam: effective especially if needed acutely
but causes fetal/ neonatal
complications(depression of muscle tone and
breath centre)

33. The EclampsiaTrial Collaborative Group
conducted two prospective trials
The primary outcome measures were the
rates of recurrent seizures and maternal
death.
Magnesium sulfate
was significantly more
effective than either diazepam or phenytoin:
Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial.
Lancet 1995; 345:1455.

34. Additional advantages ofmagnesium sulfatetherapy
include lower cost, ease of administration and less
sedation .
Magnesium also appears to selectively increase
cerebral blood flow and oxygen consumption in
women with preeclampsia
Belfort MA, MoiseKJ Jr. Effect of magnesium sulfate on maternal brain blood flow in
preeclampsia: a randomized, placebo-controlled study. Am J ObstetGynecol1992; 167:661 .

35. Cerebrovascular syndromes and preeclampsia

RCVS (postpartum
angiopathy)

RPLS


Preeclampsia,
severe

Ischemic
stroke


Reversible vasogenic
edema, subarachnoid
hemorrhage

Thunderclap
headache,
reversible cerebral
vasoconstriction


Intracerebral
hemorrhage

36. Most common causes of both ischemic and
hemorrhagic stroke in pregnancy.

The most frequent cerebrovasculardisturbance
associated with eclampsiais a reversible
encephalopathy.
Women with preeclampsia are at risk for stroke and cardiovascular disease well after the
postpartum period and child bearing years. The
relative risks ranged from 1.39 to 5.08.
B. J. Wilson, M. S. Watson, G. J. Prescott et al., “Hypertensive diseases of pregnancy and risk of
hypertension and stroke in later life: results from cohort study,”British Medical Journal, vol.
326, no. 7394, pp. 845– 849, 2003

37. -Preeclampsia/eclampsiacommonly associated
with ischemic stroke of arterial origin [36
percent])
-Intracerebralhemorrhage [55 percent]) but less
frequently with cerebral venous thrombosis (13
of 136 cases [10 percent])
Cantu-BritoC, ArauzA, AburtoY, et al. Cerebrovascular
complications during pregnancy and postpartum:
clinical and prognosis observations in 240 Hispanic women. EurJ Neurol2011; 18:819

38. Is a clinical radiologic syndrome of
heterogeneous etiologiesthat are grouped
together because of similar findings on
neuroimagingstudies
RPLS may occur in the setting of preeclampsia
due to impaired cerebral autoregulationfrom
endothelial damage.

39. Autoregulatoryfailure Endothelial dysfunction
vasodilatation capillarleakage
hyperperfusion disruption BBB
Vasogenicedeoma

40. Clinical presentation
Headaches
Altered consciousness
Visual disturbances
Seizures -are usually generalized tonic
clonic; they may begin focally.

41. Other risk factors-
Acute and chronic renal failure
Immunosuppressive agents and cytotoxicdrugs
Hemolytic and uremic syndrome
Collagen vascular disorders
leukemia
Behcetssyndrome
TTP
HIV
Acute intermittent prophyria
Hypercalcemia,hypomagnesmia
Contrast media exposure
Cryoglobulinemia

42. Some suggest that PRES (typical clinical syndrome
and neuroimagingfindings) could be considered an
indicator of eclampsia, even when the other
features of eclampsia(proteinuria, hypertension)
are not present.
Br J ObstetGynaecol1997 Oct;104(10):1165- 72

43. FLAIR images show high signal symmetrically involving bilateral
parieto-occipital, posterior frontal, and temporo- occipital regions

44. The classical presentation of RCVS, also
known as Call Fleming Syndrome, is a
thunderclap headache, with or without
additional neurologic signs.
Diagnostic imaging reveals multifocal segmental vasoconstriction of the cerebral arteries, which usually resolves within days to weeks.

45. Calcium channel blockers may be initiated,
such as nimodipineor verapamil, although
caution should be employed to maintain
cerebral perfusion in watershed regions of a
constricted artery.
The primary difference between RPLS and RCVS is in the clinical symptoms.
L.H. Calabrese, D.W. Dodick, T. J. Schwedt, and A. B. Singhal, “Narrative review: reversible cerebral
vasoconstriction syndromes,”
Annals of Internal Medicine, vol. 146, no. 1, pp. 34– 44, 2007.

46. There is nearly a 4- fold odds of developing
hypertension (OR 3.7, 95% CI 2.70–5.05)
2-fold risk of ischemic heart disease (OR
2.16, 95% CI 1.86–2.52) in women with
preeclampsia.
For fatal and nonfatal stroke, relative risks
ranged from 1.39 to 5.08.

Children may also be at increased risk for neurological problems and stroke.

47. There was a significant reduction in the rate of
preeclampsia with low dose aspirin started at 16
weeks gestation or earlier in women identified as
moderate or high risk.
Vitamin D deficiency has recently emerged as an important potentially modifiable risk factor for both preeclampsia and stroke.
E. Bujold, S. Roberge, Y. Lacasseet al., “Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early
pregnancy: a metaanalysis,”
Obstetrics and Gynecology, vol. 116, no. 2 PART 1, pp. 402–414, 2010.