What causes eclamptic seizures?

What Causes Eclamptic Seizures

Eclamptic seizures result from blood-brain barrier disruption and cerebral endothelial dysfunction, triggered by circulating placental factors released from an ischemic, poorly perfused placenta that overwhelm cerebral autoregulation and cause vasogenic edema. 1, 2

Two-Stage Pathophysiologic Mechanism

Stage 1: Placental Dysfunction

• Abnormal placentation is the initiating event, characterized by shallow cytotrophoblast invasion of maternal spiral arteries 1
• Spiral arteries fail to undergo normal remodeling—they remain small muscular vessels instead of becoming distended, low-resistance channels 1
• This remodeling failure extends only superficially into the decidua rather than deep into the myometrium, resulting in reduced placental perfusion and placental ischemia 1
• The ischemic placenta becomes the source of pathogenic factors released into maternal circulation 1

Stage 2: Maternal Syndrome and Seizure Mechanism

• The hypoxic placenta releases soluble factors into maternal blood, including excess sFlt-1 (soluble Fms-like tyrosine kinase-1), which antagonizes vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) 1
• These circulating factors cause systemic endothelial dysfunction throughout maternal vasculature, including cerebral vessels 1, 2
• Blood-brain barrier permeability increases due to these circulating factors (particularly altered VEGF and PlGF), allowing fluid, ions, and plasma proteins to pass into brain parenchyma 2
• Cerebral autoregulation fails when severe hypertension exceeds the upper limit of autoregulation (typically >160/110 mmHg), causing forced vasodilation and further endothelial injury 1, 3
• The result is vasogenic cerebral edema, predominantly in posterior circulation territories (posterior reversible encephalopathy syndrome or PRES), which lowers the seizure threshold 2, 4

Supporting Pathophysiologic Evidence

Vascular and Hemodynamic Factors

• Extensive cerebral vasculopathy develops within brain parenchyma in eclampsia 4
• The placenta releases vasoactive substances (nitric oxide, prostaglandins, endothelin) that induce platelet aggregation, endothelial dysfunction, and arterial hypertension 1
• Fibrin deposition occurs in small blood vessels throughout multiple organ systems, including cerebral vessels 1

Neurochemical Mechanisms

• Magnesium deficiency may contribute, as magnesium normally blocks neuromuscular transmission and decreases acetylcholine release at motor end-plates 5
• The seizure mechanism involves diffuse cerebral dysfunction with epileptiform activity, as demonstrated by EEG showing delta waves and spikes/sharp waves 4

Clinical Context and Risk Factors

Timing and Incidence

• Eclampsia occurs in 2% of women with severe preeclampsia who do not receive magnesium sulfate prophylaxis, versus <0.6% in those receiving it 2
• Seizures can occur antepartum (after 20 weeks gestation), intrapartum, or postpartum—rarely before 20 weeks except with gestational trophoblastic disease 1, 6

Warning Signs of Impending Seizures

• Occipital lobe blindness, hyperreflexia, and clonus indicate severe cerebrovascular involvement and high seizure risk 1, 3
• Headache and visual disturbances reflect cerebral edema 1
• Right upper quadrant/epigastric pain suggests hepatic involvement (HELLP syndrome overlap) 1

Critical Pitfall to Avoid

Do not assume eclamptic seizures are solely caused by hypertension itself—the seizures result from the underlying endothelial dysfunction and blood-brain barrier breakdown, not just elevated blood pressure numbers. This is why aggressive blood pressure lowering in the setting of cerebral edema can be harmful, as elevated pressure may be compensatory to maintain cerebral perfusion pressure 7. The multisystem nature of preeclampsia means relatively few adverse effects are actually due to hypertension alone 1.

Why the Placenta is Central

• Preeclampsia and eclampsia can occur without a fetus (as in hydatidiform mole), proving the placenta—not the fetus—is the key pathogenic component 1
• The only definitive treatment is delivery of the placenta, which removes the source of circulating pathogenic factors 1, 8
• Continuous maternal magnesium sulfate administration beyond 5-7 days can cause fetal abnormalities, but this does not change the placental origin of the maternal syndrome 5